論文 - 菱川 善隆
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HMGB2 Promotes De Novo Lipogenesis to Accelerate Hepatocyte Proliferation During Liver Regeneration. 査読あり
Choijookhuu N, Yano K, Lkham-Erdene B, Shirouzu S, Kubota T, Fidya, Ishizuka T, Kai K, Chosa E, Hishikawa Y
J. Histochem. Cytochem 72 ( 4 ) 245 - 264 2024年4月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Histochemistry and Cytochemistry
Liver regeneration is a well-orchestrated compensatory process that is regulated by multiple factors. We recently reported the importance of the chromatin protein, a high-mobility group box 2 (HMGB2) in mouse liver regeneration. However, the molecular mechanism remains unclear. In this study, we aimed to study how HMGB2 regulates hepatocyte proliferation during liver regeneration. Seventy-percent partial hepatectomy (PHx) was performed in wild-type (WT) and HMGB2-knockout (KO) mice, and the liver tissues were used for microarray, immunohistochemistry, quantitative polymerase chain reaction (qPCR), and Western blotting analyses. In the WT mice, HMGB2-positive hepatocytes colocalized with cell proliferation markers. In the HMGB2-KO mice, hepatocyte proliferation was significantly decreased. Oil Red O staining revealed the transient accumulation of lipid droplets at 12–24 hr after PHx in the WT mouse livers. In contrast, decreased amount of lipid droplets were found in HMGB2-KO mouse livers, and it was preserved until 36 hr. The microarray, immunohistochemistry, and qPCR results demonstrated that the expression of lipid metabolism–related genes was significantly decreased in the HMGB2-KO mouse livers. The in vitro experiments demonstrated that a decrease in the amount of lipid droplets correlated with decreased cell proliferation activity in HMGB2-knockdown cells. HMGB2 promotes de novo lipogenesis to accelerate hepatocyte proliferation during liver regeneration:
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Ikenoue M, Choijookhuu N, Yano K, Fidya, Takahashi N, Ishizuka T, Shirouzu S, Yamaguma Y, Kai K, Higuchi K, Sawaguchi A, Nanashima A, Hishikawa Y.
Histochem Cell Biol 161 ( 4 ) 325 - 336 2024年4月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Histochemistry and Cell Biology
Su (var) 3–9, enhancer of seste, trithorax (SET)-domain bifurcated histone lysine methyltransferase (SETDB1) plays a crucial role in maintaining intestinal stem cell homeostasis; however, its physiological function in epithelial injury is largely unknown. In this study, we investigated the role of SETDB1 in epithelial regeneration using an intestinal ischemia/reperfusion injury (IRI) mouse model. Jejunum tissues were sampled after 75 min of ischemia followed by 3, 24, and 48 h of reperfusion. Morphological evaluations were performed using light microscopy and electron microscopy, and the involvement of SETDB1 in epithelial remodeling was investigated by immunohistochemistry. Expression of SETDB1 was increased following 24 h of reperfusion and localized in not only the crypt bottom but also in the transit amplifying zone and part of the villi. Changes in cell lineage, repression of cell adhesion molecule expression, and decreased histone H3 methylation status were detected in the crypts at the same time. Electron microscopy also revealed aberrant alignment of crypt nuclei and fusion of adjacent villi. Furthermore, increased SETDB1 expression and epithelial remodeling were confirmed with loss of stem cells, suggesting SETDB1 affects epithelial cell plasticity. In addition, crypt elongation and increased numbers of Ki-67 positive cells indicated active cell proliferation after IRI; however, the expression of PCNA was decreased compared to sham mouse jejunum. These morphological changes and the aberrant expression of proliferation markers were prevented by sinefungin, a histone methyltransferase inhibitor. In summary, SETDB1 plays a crucial role in changes in the epithelial structure after IRI-induced stem cell loss.
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Choijookhuu N, Shibata Y, Ishizuka T, Xu Y, Koji T, Hishikawa Y
Acta Histochemica et Cytochemica. 2022 October 25;55(5):119-128 55 ( 5 ) 119 - 128 2022年10月
担当区分：最終著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Acta Histochemica et Cytochemica
In situ hybridization (ISH) is a powerful method for detecting specific RNAs at the cellular level. Although conventional ISH using hapten-labeled probes are useful for detecting multiple RNAs, the detection procedures are still complex and required longer time. Therefore, we introduced a new application of fluorescence resonance energy transfer (FRET)-based molecular beacon (MB) probes for ISH. MCF-7 cells and C57BL/6J mouse uterus were used for ISH. MB probes for ERα mRNA and 28S rRNA were labeled with Cy3/BHQ-2 and 6-FAM/ DABCYL, and conventional probes were labeled with digoxigenin. Fluorescence measure-ments revealed that of more-rapid hybridization kinetics compared to conventional probes. In MCF-7 cells, 28S rRNA was detected in nucleolus and cytoplasm of all cells, whereas ERα mRNA was detected in some nucleolus. In the uterus, 28S rRNA was clearly detected using complementary MB probe, but there were no signals in control slides. Moreover, 28S rRNA was detected in all cells, whereas ERα mRNA was detected mainly in the epithelium. Fluorescence intensity of 28S rRNA was decreased significantly in 1 or 2 base-mismatched sequences, that indicates highly specific detection of target RNAs. In conclusion, the FRET-based MB probes are very useful for ISH, providing rapid hybridization, high sensitivity and specificity.
DOI： 10.1267/ahc.22-00075
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Yamaguma Y, Sugita N, Choijookhuu N, Yano K, Lee D, Ikenoue M, Fidya, Shirouzu S, Ishizuka T, Tanaka M, Yamashita Y, Chosa E, Taniguchi N, Hishikawa Y
Histochemistry and Cell Biology. 2022 Mar;157(3):359-369 157 ( 3 ) 359 - 369 2022年3月
担当区分：最終著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Histochemistry and Cell Biology
High-mobility group box 2 (HMGB2) is a chromatin-associated protein that is an important regulator of gene transcription, recombination, and repair processes. The functional importance of HMGB2 has been reported in various organs, including the testis, heart, and cartilage. However, its role in the ovary is largely unknown. In this study, ovary tissues from wild-type (WT) and HMGB2-knock-out (KO) mice were examined by histopathological staining and immunohistochemistry. The ovary size and weight were significantly lower in HMGB2-KO mice than in age-matched WT littermates. Histopathological analysis revealed ovarian atrophy and progressive fibrosis in 10-month-old HMGB2-KO mouse ovaries. Compared to age-matched WT mice, the numbers of oocytes and developing follicles were significantly decreased at 2 months of age and were completely depleted at 10 months of age in HMGB2-KO mice. Immunohistochemistry revealed the expression of HMGB2 in the granulosa cells of developing follicles, oocytes, some corpora lutea, and stromal cells. Importantly, HMGB2-positive cells were co-localized with estrogen receptor beta (ERβ), but not ERα. Estrogen response element-binding activity was demonstrated by southwestern histochemistry, and it was decreased in HMGB2-KO mouse ovaries. Cell proliferation activity was also decreased in HMGB2-KO mouse ovaries in parallel with the decreased folliculogenesis. These results indicated that the depletion of HMGB2 induced ovarian atrophy that was characterized by a decreased ovarian size and weight, progressive fibrosis, as well as decreased oocytes and folliculogenesis. In conclusion, we demonstrated the crucial role of HMGB2 in mouse ovarian folliculogenesis through ERβ expression.
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Sugita N, Choijookhuu N, Yano K, Lee D, Ikenoue M, Fidya, Taniguchi N, Chosa E, Hishikawa Y
Biology of reproduction ;105(6) 105 ( 6 ) 1510 - 1520 2021年10月
担当区分：最終著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Biology of Reproduction
High-mobility group box 2, a chromatin-associated protein that interacts with deoxyribonucleic acid, is implicated in multiple biological processes, including gene transcription, replication, and repair. High-mobility group box 2 is expressed in several tissues, including the testis; however, its functional role is largely unknown. Here, we elucidated the role of high-mobility group box 2 in spermatogenesis. Paraffin-embedded testicular tissues were obtained from 8-week-old and 1-year-old wild-type and knock-out mice. Testis weight and number of seminiferous tubules were decreased, whereas atrophic tubules were increased in high-mobility group box 2-depleted mice. Immunohistochemistry revealed that atrophic tubules contained Sertoli cells, but not germ cells. Moreover, decreased cell proliferation and increased apoptosis were demonstrated in high-mobility group box 2-depleted mouse testis. To elucidate the cause of tubule atrophy, we examined the expression of androgen and estrogen receptors, and the results indicated aberrant expression of androgen receptor and estrogen receptor alpha in Sertoli and Leydig cells. Southwestern histochemistry detected decreased estrogen response element–binding sites in high-mobility group box 2-depleted mouse testis. High-mobility group box 1, which has highly similar structure and function as high-mobility group box 2, was examined by immunohistochemistry and western blotting, which indicated increased expression in testis. These findings indicate a compensatory increase in high-mobility group box 1 expression in high-mobility group box 2 knock-out mouse testis. In summary, depletion of high-mobility group box 2 induced aberrant expression of androgen receptor and estrogen receptor alpha, leading to decreased germ cell proliferation and increased apoptosis which resulted in focal seminiferous tubule atrophy.
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Non-Cytotoxic Photodynamic Therapy with Talaporfin Sodium Reduces the Expression of CXCR4 and Enhances Chemotherapeutic Efficacy in Undifferentiated Gastric Cancer Cell Line HGC27 査読あり
Kai Kengo, Ishizuka Takumi, Matsumoto Jin, Shimamawari Koki, Mori Ryoma, Fidya, Lkham-Erdene Baljinnyam, Kubota Toshiki, Ikenoue Makoto, Higuchi Kazuhiro, Nanashima Atsushi, Hishikawa Yoshitaka
Ａｃｔａ Ｈｉｓｔｏｃｈｅｍｉｃａ ｅｔ Ｃｙｔｏｃｈｅｍｉｃａ 58 ( 2 ) 69 - 79 2025年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：日本組織細胞化学会
Gastric cancer (GC), particularly the undifferentiated type, is frequently associated with peritoneal metastasis, which significantly worsens prognosis due to its resistance to conventional treatments. Photodynamic therapy (PDT) is localized treatment using a photosensitizer (PS) activated by light of a specific wavelength to generate cytotoxic reactive oxygen species that induce cell death. Severe adverse events were reported from clinical trials investigating PDT for peritoneal dissemination conducted until the early 2000s, leaving its safety and clinical effectiveness unestablished. The present study explored whether “non-cytotoxic” PDT using talaporfin sodium (TS) could enhance efficacy of chemotherapeutic agents in undifferentiated GC cell line HGC27. Cell viability was evaluated with MTT assay following TS-PDT, and the synergistic effect between non-cytotoxic TS-PDT and anticancer drug SN-38 was assessed. Changes in expression of drug resistance markers were analyzed through qRT-PCR, Western blotting, and immunocytochemistry. We found that non-cytotoxic TS-PDT enhanced the efficacy of chemotherapy in the undifferentiated GC cell line and reduced the expression of C-X-C chemokine receptor type 4, a key marker associated with GC stem-like properties. These findings highlight the potential of non-cytotoxic TS-PDT as a synergistic treatment approach. We conclude that non-cytotoxic TS-PDT could enhance drug sensitivity and offers a promising therapeutic strategy for GC.
DOI： 10.1267/ahc.25-00002
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Non-Cytotoxic Photodynamic Therapy with Talaporfin Sodium Reduces the Expression of CXCR4 and Enhances Chemotherapeutic Efficacy in Undifferentiated Gastric Cancer Cell Line HGC27. 査読あり
Kengo Kai, Takumi Ishizuka, Jin Matsumoto, Koki Shimamawari, Ryoma Mori, Fidya, Baljinnyam Lkham-Erdene, Toshiki Kubota, Makoto Ikenoue, Kazuhiro Higuchi, Atsushi Nanashima, Yoshitaka Hishikawa
Acta Histochem. Cytochem 2025年3月
担当区分：責任著者 掲載種別：研究論文（学術雑誌）
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Kazuhiro Higuchi, Makoto Ikenoue, Takumi Ishizuka, Kengo Kai, Nobuyasu Takahashi, Toshiki Kubota, Shinichiro Shirouzu, Baljinnyam Lkham-Erdene, Kham Mo Aung, Michikazu Nakai, Akira Sawaguchi, Atsushi Nanashima, Yoshitaka Hishikawa
Acta Histochem. Cytochem 58 ( 1 ) 9 - 18 2025年2月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Acta Histochemica et Cytochemica
SET domain bifurcated 1 (SETDB1), a histone H3K9-specific methyltransferase, is crucial for heterochromatin formation and intestinal homeostasis, but its role in intestinal ischemia-reperfusion injury (IRI) remains unclear. This study investigated changes in SETDB1-mediated nuclear chromatin regulation in intestinal epithelial cells (IECs) using an IRI mouse model. Jejunal samples were collected after 75 min of ischemia followed by 24 hr of reperfusion. Sinefungin was administered as a histone methyltransferase inhibitor. Morphologic changes were evaluated using hematoxylin-eosin staining and electron microscopy, and cell-adhesion molecule expression, including ZO-1, E-cadherin, integrin-β4, and laminin, was evaluated using immunohistochemistry. Super-resolution microscopy analyzed intranuclear SETDB1 localization and heterochromatin formation in IECs. IRI-affected jejunum exhibited massive IEC detachment, dilated intercellular spaces, basement membrane damage, and decreased expression of E-cadherin and integrin-β4. Sinefungin prevented these changes, however. The proportion of IECs expressing nuclear SETDB1 throughout the euchromatin was significantly higher in IRI-affected jejunum (77.8%) than sham-treated (3.0%) or sinefungin-treated, IRI-affected jejunum (2.7%). The proportion of IECs with decreased heterochromatin was significantly higher in sinefungin-treated, IRI-affected jejunum (84.3%) than untreated IRI-affected jejunum (15.6%). These findings suggest that SETDB1-mediated chromatin regulation is pivotal in intestinal IRI and represents a potential therapeutic target.
DOI： 10.1267/ahc.24-00061
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Baljinnyam Lkham-Erdene, Choijookhuu N, Kubota T, Uto T, Mitoma S, Shirouzu S, Ishizuka T, Kai K, Higuchi K, Aung K, Batmunkh J, Sato K, Hishikawa Y
Acta Histochem. Cytochem 57 ( 5 ) 175 - 188 2024年10月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Acta Histochemica et Cytochemica
Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming a major health problem worldwide. Liver regeneration is crucial for restoring liver function, and is regulated by extraordinary complex process, involving numerous factors under both physiologic and pathologic conditions. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid synthesized by sphingosine kinase 1 (SphK1), plays an important role in liver function through S1P receptors (S1PRs)-expressing cells. In this study, we investigated the effect of lipid overload on hepatocyte proliferation in a mouse hepatic steatosis model induced by feeding a methionine-and choline-deficient (MCD) diet. After 50% partial hepatectomy (PHx), liver tissues were sampled at various timepoints and then analyzed by immunohistochemistry, oil Red-O staining, quantitative-polymerase chain reaction (qPCR), and flow cytometry. In mice fed the MCD-diet, significantly exacerbated hepatic steatosis and accelerated liver regeneration were observed. After PHx, hepatocyte proliferation peaked at 48 and 36 hr in the liver of chow-and MCD-diet fed mice, respectively. By contrast, increased expression of S1PR2 was observed in hepatic neutrophils and macrophages of MCD-diet fed mice. Flow cytome-try and qPCR experiments demonstrated that levels of HGF and FGF2 released by neutrophils and macrophages were significantly higher in MCD-diet fed mice. In conclusion, hepatic lipid overload recruits Kupffer cells and neutrophils that release HGF and FGF2 via SphK1/S1PR2 activation to accelerate hepatocyte proliferation.
DOI： 10.1267/ahc.24-00046
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Acceptance of Virtual Reality Simulation Training for Stoma Care by Healthcare Providers: A Pilot Questionnaire Study After Viewing Prototype Imagings. 査読あり
Kai K, Shinoda H, Takeiri E, Hamada T, Chikubu M, Kodama Y, Higuchi K, Nanashima A
Cureus 2024年7月
担当区分：責任著者 掲載種別：研究論文（学術雑誌）
DOI： 10.7759/cureus.65465
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蛍光共鳴エネルギー移動（FRET）現象を利用した高感度<i>in situ</i> hybridization 査読あり
石塚 匠, 柴田 恭明, 小路 武彦, 菱川 善隆
顕微鏡 58 ( 3 ) 117 - 122 2023年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：公益社団法人 日本顕微鏡学会
代表的な組織学的手法の一つである<i>in situ</i> hybridization法（ISH）は，組織切片上で特異的な塩基配列を有する核酸分子を視覚化し，「本来存在する場所（<i>in situ</i>）」で検出する方法である．ISHは多様な細胞により構成されている組織内で特定の遺伝子を同定するための方法論として，分子機構の解明や疾患の病態解明に貢献している．一方で，プローブや標識の種類などによっては検出感度が十分でない場合がある．本稿では，蛍光共鳴エネルギー移動（Fluorescence Resonance Energy Transfer: FRET）現象を利用した高感度蛍光標識プローブを用いたFRET based <i>in situ</i> hybridization（FRET-ISH）について紹介する．
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Protective role of estrogen through G-protein coupled receptor 30 in a colitis mouse model. 査読あり
Fidya, Choijookhuu N, Ikenoue M, Yano K, Yamaguma Y, Shirouzu S, Kai K, Ishizuka T, Hishikawa Y
Histochem Cell Biol 161 ( 1 ) 81 - 93 2023年10月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Histochemistry and Cell Biology
Estrogen and its receptors are involved in the pathogenesis of gastrointestinal diseases such as colitis. However, the role of the membrane estrogen receptor G-protein-coupled receptor 30 (GPR30) in colitis is poorly understood. We therefore investigated the effect of estrogen in dextran sulfate sodium (DSS)-induced colitis. Male C57BL/6 mice were administered 1.5% DSS for 5 days and treated with 17β-estradiol (E2), GPR30 agonist (G1), or GPR30 antagonist (G15) for 8 days. Inflammation grade was evaluated by disease activity index (DAI) and histomorphological score. Colon tissues were immunohistochemically analyzed and revealed high expression of membrane GPR30, histone 3 lysine 36 dimethylation, and lysine 79 trimethylation in normal mouse colon epithelial cells but significantly decreased expression in DSS-treated mice, whereas the expression was partially preserved after treatment with E2 or G1. Colon shortening and DAI were significantly lower in E2- and G1-treated mice compared to DSS-treated mice. Caudal type homeobox 2 (CDX2) expression and cell proliferation differed in normal colon epithelial cells but overlapped in those of DSS-treated mice. Administration of E2 and G1 reduced CDX2 expression and cell proliferation. Altered expression of claudin-2 and occludin were observed in the colonic epithelium of DSS-treated mice, and these changes were significantly lower in the colon of E2- and G1-treated mice. These results indicate that estrogen regulates histone modification, cell proliferation, and CDX2 expression through GPR30, which affects intestinal epithelial barrier function. We conclude that estrogen protects against intestinal epithelial damage through GPR30 by enhancing intestinal epithelial barrier function in DSS-induced colitis in mice.
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Tmem161a regulates bone formation and bone strength through the P38 MAPK pathway. 査読あり
Nagai T, Sekimoto T, Kurogi S, Ohta T, Miyazaki S, Yamaguchi Y, Tajima T, Chosa E, Imasaka M, Yoshinobu K, Araki K, Araki M, Choijookhuu N, Sato K, Hishikawa Y, Funamoto T
Sci Rep 13 ( 1 ) 14639 2023年9月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
Bone remodeling is an extraordinarily complex process involving a variety of factors, such as genetic, metabolic, and environmental components. Although genetic factors play a particularly important role, many have not been identified. In this study, we investigated the role of transmembrane 161a (Tmem161a) in bone structure and function using wild-type (WT) and Tmem161a-depleted (Tmem161aGT/GT) mice. Mice femurs were examined by histological, morphological, and bone strength analyses. Osteoblast differentiation and mineral deposition were examined in Tmem161a-overexpressed, -knockdown and -knockout MC3T3-e1 cells. In WT mice, Tmem161a was expressed in osteoblasts of femurs; however, it was depleted in Tmem161aGT/GT mice. Cortical bone mineral density, thickness, and bone strength were significantly increased in Tmem161aGT/GT mice femurs. In MC3T3-e1 cells, decreased expression of alkaline phosphatase (ALP) and Osterix were found in Tmem161a overexpression, and these findings were reversed in Tmem161a-knockdown or -knockout cells. Microarray and western blot analyses revealed upregulation of the P38 MAPK pathway in Tmem161a-knockout cells, which referred as stress-activated protein kinases. ALP and flow cytometry analyses revealed that Tmem161a-knockout cells were resistant to oxidative stress. In summary, Tmem161a is an important regulator of P38 MAPK signaling, and depletion of Tmem161a induces thicker and stronger bones in mice.
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Kai K, Nakashima K, Kawakami H, Takeno S, Hishikawa Y, Ikenoue M, Hamada T, Imamura N, Shibata T, Noritomi T, Sasaki F, Nakamura Y, Nanashima A
Intern Med 63 ( 7 ) 903 - 910 2023年8月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Internal Medicine
Introduction Photodynamic therapy (PDT) is a salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Salvage PDT is the treatment available for vulnerable patients with various comorbidities at risk of salvage esophagectomy. This study assessed the impact of the Charlson comorbidity index (CCI) on the outcomes of salvage PDT using talaporfin sodium (TS) for esophageal cancer. Metohds Consecutive patients with esophageal cancer who underwent salvage TS-PDT from 2016 to 2022 were included in this retrospective study. We investigated the local complete response (L-CR), progressionfree survival (PFS) and overall survival (OS) and evaluated the relationship between the CCI and therapeutic efficacy. Results In total, 25 patients were enrolled in this study. Overall, 12 patients (48%) achieved an L-CR, and the 2-year PFS and OS rates were 24.9% and 59.4%, respectively. In a multivariate analysis, a CCI ≥1 (p= 0.041) and deeper invasion (p=0.048) were found to be significant independent risk factors for not achieving an L-CR. To evaluate the efficacy associated with comorbidities, we divided the patients into the CCI=0 group (n=11) and the CCI ≥1 group (n=14). The rate of an L-CR (p=0.035) and the 2-year PFS (p=0.029) and OS (p=0.018) rates in the CCI ≥1 group were significantly lower than those in the CCI=0 group. Conclusion This study found that the CCI was negatively associated with the efficacy of salvage TS-PDT for esophageal cancer.
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Clec4A4 Acts As A Negative Immune Checkpoint Regulator to Suppress Antitumor Immunity.
Uto T, Fukaya T, Mitoma S, Nishikawa Y, Tominaga M, Choijookhuu N, Hishikawa Y, Sato K
Cancer immunology research 11 ( 9 ) 1266 - 1279 2023年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cancer Immunology Research
Clec4A4 is a C-Type lectin receptor (CLR) exclusively expressed on murine conventional dendritic cells (cDC) to regulate their activation status. However, the functional role of murine Clec4A4 (mClec4A4) in antitumor immunity remains unclear. Here, we show that mClec4A4 serves as a negative immune checkpoint regulator to impair antitumor immune responses. Deficiency of mClec4A4 lead to a reduction in tumor development, accompanied by enhanced antitumor immune responses and amelioration of the immunosuppressive tumor microenvironment (TME) mediated through the enforced activation of cDCs in tumor-bearing mice. Furthermore, antagonistic mAb to human CLEC4A (hCLEC4A), which is the functional orthologue of mClec4A4, exerted protection against established tumors without any apparent signs of immunerelated adverse events in hCLEC4A-Transgenic mice. Thus, our findings highlight the critical role of mClec4A4 expressed on cDCs as a negative immune checkpoint molecule in the control of tumor progression and provide support for hCLEC4A as a potential target for immune checkpoint blockade in tumor immunotherapy.
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Fukaya T., Uto T., Mitoma S., Takagi H., Nishikawa Y., Tominaga M., Choijookhuu N., Hishikawa Y., Sato K.
Cell Reports 42 ( 5 ) 112431 2023年5月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cell Reports
While dysbiosis in the gut is implicated in the impaired induction of oral tolerance generated in mesenteric lymph nodes (MesLNs), how dysbiosis affects this process remains unclear. Here, we describe that antibiotic-driven gut dysbiosis causes the dysfunction of CD11c+CD103+ conventional dendritic cells (cDCs) in MesLNs, preventing the establishment of oral tolerance. Deficiency of CD11c+CD103+ cDCs abrogates the generation of regulatory T cells in MesLNs to establish oral tolerance. Antibiotic treatment triggers the intestinal dysbiosis linked to the impaired generation of colony-stimulating factor 2 (Csf2)-producing group 3 innate lymphoid cells (ILC3s) for regulating the tolerogenesis of CD11c+CD103+ cDCs and the reduced expression of tumor necrosis factor (TNF)-like ligand 1A (TL1A) on CD11c+CD103+ cDCs for generating Csf2-producing ILC3s. Thus, antibiotic-driven intestinal dysbiosis leads to the breakdown of crosstalk between CD11c+CD103+ cDCs and ILC3s for maintaining the tolerogenesis of CD11c+CD103+ cDCs in MesLNs, responsible for the failed establishment of oral tolerance.
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Dispensable role of Rac1 and Rac3 after cochlear hair cell specification. 査読あり
Nakamura T, Sakaguchi H, Mohri H, Ninoyu Y, Goto A, Yamaguchi T, Hishikawa Y, Matsuda M, Saito N, Ueyama T
Journal of molecular medicine (Berlin, Germany) 101 ( 7 ) 843 - 854 2023年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Molecular Medicine
Abstract: Rac small GTPases play important roles during embryonic development of the inner ear; however, little is known regarding their function in cochlear hair cells (HCs) after specification. Here, we revealed the localization and activation of Racs in cochlear HCs using GFP-tagged Rac plasmids and transgenic mice expressing a Rac1-fluorescence resonance energy transfer (FRET) biosensor. Furthermore, we employed Rac1-knockout (Rac1-KO, Atoh1-Cre;Rac1 flox/flox) and Rac1 and Rac3 double KO (Rac1/Rac3-DKO, Atoh1-Cre;Rac1 flox/flox ;Rac3 −/−) mice, under the control of the Atoh1 promoter. However, both Rac1-KO and Rac1/Rac3-DKO mice exhibited normal cochlear HC morphology at 13 weeks of age and normal hearing function at 24 weeks of age. No hearing vulnerability was observed in young adult (6-week-old) Rac1/Rac3-DKO mice even after intense noise exposure. Consistent with prior reports, the results from Atoh1-Cre;tdTomato mice confirmed that the Atoh1 promoter became functional only after embryonic day 14 when the sensory HC precursors exit the cell cycle. Taken together, these findings indicate that although Rac1 and Rac3 contribute to the early development of sensory epithelia in cochleae, as previously shown, they are dispensable for the maturation of cochlear HCs in the postmitotic state or for hearing maintenance following HC maturation. Key messages: Mice with Rac1 and Rac3 deletion were generated after HC specification.Knockout mice exhibit normal cochlear hair cell morphology and hearing.Racs are dispensable for hair cells in the postmitotic state after specification.Racs are dispensable for hearing maintenance after HC maturation.
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Kai K., Hamada T., Sato Y., Hiyoshi M., Imamura N., Yano K., Ikeda T., Ichihara A., Ogata S., Choijookhuu N., Hishikawa Y., Hosokawa A., Nanashima A.
Journal of Oncology 2023 1440257 - 8 2023年3月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Oncology
Background. Oxaliplatin (OX)-based chemotherapy induces sinusoidal obstruction syndrome (SOS) in the nontumorous liver parenchyma, which can increase the risk of liver resection due to colorectal liver metastasis (CRLM). The extracellular volume (ECV) calculated from contrast-enhanced computed tomography (CT) has been reported to reflect the morphological change of hepatic fibrosis. The present retrospective study aimed to evaluate the ECV fraction as a predictive factor for OX-induced SOS. Methods. Our study included 26 patients who underwent liver resection for CRLM after OX-based chemotherapy with a preoperative dynamic CT of appropriate quality. We investigated the relationship between the pathological SOS grade and the ECV fraction. Results. Overall, 26 specimens from the patients were graded with the SOS classification of Rubbia-Brandt et al. as follows: grade 0, n = 17 (65.4%); grade 1, n = 4 (15.4%); and grade 2, n = 5 (19.2%). No specimens showed grade 3 SOS. In a univariate analysis, the ECV fraction in grade 0 SOS was significantly lower than that in grade 1 + 2 SOS (26.3 ± 3.4% vs. 30.6 ± 7.0%; P = 0.025). The cutoff value and AUC value of the ECV fraction to distinguish between grades 0 and 1 + 2 were 27.5% and 0.771, respectively. Conclusions. Measurement of the ECV fraction was found to be a potential noninvasive diagnostic method for determining early-stage histopathological sinusoidal injury induced by OX-based chemotherapy.
DOI： 10.1155/2023/1440257
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Correction: Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility.
Shirouzu S, Sugita N, Choijookhuu N, Yamaguma Y, Takeguchi K, Ishizuka T, Tanaka M, Fidya, Kai K, Chosa E, Yamashita Y, Koshimoto C, Hishikawa Y
Journal of ovarian research 16 ( 1 ) 21 2023年1月
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Kai K., Hiyoshi M., Imamura N., Hamada T., Yano K., Sato Y., Sakae T., Komi M., Nakamura T., Choijookhuu N., Hishikawa Y., Nanashima A.
Internal Medicine 62 ( 8 ) 1107 - 1115 2023年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Internal Medicine
Objective The extracellular volume (ECV) calculated based on contrast-enhanced computed tomography (CT) has been reported as a novel imaging parameter reflecting the morphological change of fibrosis in several parenchymal organs. Our retrospective study assessed the validity of the ECV fraction for diagnosing pancreatic fibrosis and the appropriate imaging condition as the “equilibrium phase”. Methods In 27 patients undergoing multiphasic CT and subsequent pancreaticoduodenectomy, we investigated pathological fibrotic changes related to the ECV fraction and conducted analyses using the value obtained by subtracting the equilibrium CT value of the portal vein from that of the abdominal aorta (AoPVequilibrium) to estimate eligibility of the equilibrium phase. Results In all patients, the ECV fraction showed a weak positive correlation with the collagenous compartment ratio (r=0.388, p=0.045). All patients were divided into two groups - the high-Ao-PVequilibrium group and low-Ao-PVequilibrium group - based on the median value. No significant correlation was found in the high-Ao-PVequilibrium group, whereas a significant correlation was observed in the low-Ao-PVequilibrium group (r=0.566, p= 0.035). Conclusion The ECV fraction is a possible predictive factor for histopathological pancreatic fibrosis. In its clinical application, the eligibility of the “equilibrium phase” may affect the diagnostic capability. It will be necessary to verify the imaging conditions in order to improve the accuracy of the diagnosis.
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Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility 査読あり
Shirouzu S, Sugita N, Choijookhuu N, Yamaguma Y, Takeguchi K, Ishizuka T, Tanaka M, Fidya, Kai K, Chosa E, Yamashita Y, Koshimoto C, Hishikawa Y.
Journal of Ovarian Research 15 ( 1 ) 133 - 133 2022年12月
担当区分：最終著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Ovarian Research
Background: High-Mobility Group Box 1 (HMGB1) and HMGB2 are chromatin-associated proteins that belong to the HMG protein family, and are involved in the regulation of DNA transcription during cell differentiation, proliferation and regeneration in various tissues. However, the role of HMGB2 in ovarian folliculogenesis is largely unknown. Methods: We investigated the functional role of HMGB1 and HMGB2 in ovarian folliculogenesis and fertilization using C57BL/6 wild type (WT) and HMGB2-knockout (KO) mice. Ovarian tissues were obtained from WT and HMGB2-KO mice at postnatal days 0, 3, 7, and 2, 6 months of age, then performed immunohistochemistry, qPCR and Western blotting analyses. Oocyte fertilization capability was examined by natural breeding and in vitro fertilization experiments. Results: In HMGB2-KO mice, ovary weight was decreased due to reduced numbers of oocytes and follicles. Natural breeding and in vitro fertilization results indicated that HMGB2-KO mice are subfertile, but not sterile. Immunohistochemistry showed that oocytes expressed HMGB2, but not HMGB1, in neonatal and adult WT ovaries. Interestingly, in HMGB2-KO ovaries, a compensatory increase in HMGB1 was found in oocyte nuclei of neonatal and 2-month-old mice; however, this was lost at 6 months of age. Conclusions: The depletion of HMGB2 led to alterations in ovarian morphology and function, suggesting that HMGB2 plays an essential role in ovarian development, folliculogenesis and fertilization.
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Yano K., Choijookhuu N., Ikenoue M., Fidya , Fukaya T., Sato K., Lee D., Taniguchi N., Chosa E., Nanashima A., Hishikawa Y.
Scientific Reports 12 ( 1 ) 11962 2022年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
Liver regeneration is an extraordinarily complex process involving a variety of factors; however, the role of chromatin protein in hepatocyte proliferation is largely unknown. In this study, we investigated the functional role of high-mobility group box 2 (HMGB2), a chromatin protein in liver regeneration using wild-type and HMGB2-knockout (KO) mice. Liver tissues were sampled after 70% partial hepatectomy (PHx), and analyzed by immunohistochemistry, western blotting and flow cytometry using various markers of cell proliferation. In WT mice, hepatocyte proliferation was strongly correlated with the spatiotemporal expression of HMGB2; however, cell proliferation was significantly delayed in hepatocytes of HMGB2-KO mice. Quantitative PCR demonstrated that cyclin D1 and cyclin B1 mRNAs were significantly decreased in HMGB2-KO mice livers. Interestingly, hepatocyte size was significantly larger in HMGB2-KO mice at 36–72 h after PHx, and these results suggest that hepatocyte hypertrophy appeared in parallel with delayed cell proliferation. In vitro experiments demonstrated that cell proliferation was significantly decreased in HMGB2-KO cells. A significant delay in cell proliferation was also found in HMGB2-siRNA transfected cells. In summary, spatiotemporal expression of HMGB2 is important for regulation of hepatocyte proliferation and cell size during liver regeneration.
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He Z, Ishizuka T, Hishikawa Y, Xu Y
Chem Commun. 2022 Nov;58:12479-12482 58 ( 89 ) 12479 - 12482 2022年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Chemical Communications
In the present study, we synthesized a novel near-infrared turn-on BODIPY probe and a new norbornene-modified glucosamine derivative. The probe exhibits a significant NIR fluorescence emission with a turn-on response and can perform tumour-specific imaging in tumour-bearing mice. The non-natural glucosamine provides metabolic glycoengineering labelling. It can be expressed on cells as chemical tags and further reacted with fluorescence dyes for cell labelling. The combination of the two derivatives enables quick and sensitive cell imaging in vitro and in vivo using the iEDDA reaction.
DOI： 10.1039/d2cc05359d
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ヨーロッパモリネズミ（Apodemus sylvaticus）の誘起排卵卵子及び卵胞卵子の蛍光免疫染色による形態的解析 査読あり
竹口 加那子, Narantsog Choijookhuu, 名倉 悟郎, 篠原 明男, 菱川 善隆, 越本 知大
九州実験動物雑誌 38 31 - 33 2022年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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小松 弘幸, 宮内 俊一, 安倍 弘生, 舩元 太郎, 中村 仁彦, 黒木 純, 中村 佳菜子, 舟橋 美保子, 桑津 あゆみ, 菱川 善隆
宮崎県医師会医学会誌 46 ( 2 ) 197 - 202 2022年9月
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Miyazaki S., Funamoto T., Sekimoto T., Kurogi S., Ohta T., Nagai T., Tajima T., Imasaka M., Yoshinobu K., Araki K., Araki M., Choijookhuu N., Hishikawa Y., Chosa E.
Acta Histochemica et Cytochemica 55 ( 3 ) 99 - 110 2022年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Acta Histochemica et Cytochemica
Epithelial protein lost in neoplasm (EPLIN) is an actin-associated cytoskeletal protein that plays an important role in epithelial cell adhesion. EPLIN has two isoforms: EPLINα and EPLINβ. In this study, we investigated the role of EPLINβ in osteoblasts using EPLINβ-deficient (EPLINβGT/GT) mice. The skeletal phenotype of EPLINβGT/GT mice is indistinguish-able from the wildtype (WT), but bone properties and strength were significantly decreased compared with WT littermates. Histomorphological analysis revealed altered organization of bone spicules and osteoblast cell arrangement, and decreased alkaline phosphatase activity in EPLINβGT/GT mouse bones. Transmission electron microscopy revealed wider intercellular spaces between osteoblasts in EPLINβGT/GT mice, suggesting aberrant cell adhesion. In EPLINβGT/GT osteoblasts, α-and β-catenins and F-actin were observed at the cell mem-brane, but OB-cadherin was localized at the perinuclear region, indicating that cadherin-catenin complexes were not formed. EPLINβ knockdown in MC3T3-e1 osteoblast cells showed similar results as in calvaria cell cultures. Bone formation markers, such as RUNX2, Osterix, ALP, and Col1a1 mRNA were reduced in EPLINβ knockdown cells, suggesting an important role for EPLINβ in osteoblast formation. In conclusion, we propose that EPLINβ is involved in the assembly of cadherin-catenin complexes in osteoblasts and affects bone formation.
DOI： 10.1267/ahc.22-00027
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FISH・ISH
菱川 善隆, チョウジョウフ ナランツオツク
病理と臨床 がんゲノム医療時代の分子腫瘍学 臨時増刊号 40 41 - 46 2022年4月
掲載種別：研究論文（学術雑誌）
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In situ strategy for biomedical target localization via nanogold nucleation and secondary growth 査読あり
Sawaguchi A., Kamimura T., Takahashi N., Yamashita A., Asada Y., Imazato H., Aoyama F., Wakui A., Sato T., Choijookhuu N., Hishikawa Y.
Communications Biology 4 ( 1 ) 710 2021年6月
担当区分：最終著者, 責任著者 記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Communications Biology
Immunocytochemistry visualizes the exact spatial location of target molecules. The most common strategy for ultrastructural immunocytochemistry is the conjugation of nanogold particles to antibodies as probes. However, conventional nanogold labelling requires time-consuming nanogold probe preparation and ultrathin sectioning of cell/tissue samples. Here, we introduce an in situ strategy involving nanogold nucleation in immunoenzymatic products on universal paraffin/cryostat sections and provide unique insight into nanogold development under hot-humid air conditions. Nanogold particles were specifically localized on kidney podocytes to target synaptopodin. Transmission electron microscopy revealed secondary growth and self-assembly that could be experimentally controlled by bovine serum albumin stabilization and phosphate-buffered saline acceleration. Valuable retrospective nanogold labelling for gastric H+/K+-ATPase was achieved on vintage immunoenzymatic deposits after a long lapse of 15 years (i.e., 15-year-old deposits). The present in situ nanogold labelling is anticipated to fill the gap between light and electron microscopy to correlate cell/tissue structure and function.
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Nishikawa Y, Fukaya T, Fukui T, Uto T, Takagi H, Nasu J, Miyanaga N, Riethmacher D, Choijookhuu N, Hishikawa Y, Amano M, Sato K.
eCollection 12 712676 2021年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Frontiers in Immunology
Atopic dermatitis (AD) is a common pruritic inflammatory skin disease characterized by impaired epidermal barrier function and dysregulation of Thelper-2 (TH2)-biased immune responses. While the lineage of conventional dendritic cells (cDCs) are implicated to play decisive roles in T-cell immune responses, their requirement for the development of AD remains elusive. Here, we describe the impact of the constitutive loss of cDCs on the progression of AD-like inflammation by using binary transgenic (Tg) mice that constitutively lacked CD11chi cDCs. Unexpectedly, the congenital deficiency of cDCs not only exacerbates the pathogenesis of AD-like inflammation but also elicits immune abnormalities with the increased composition and function of granulocytes and group 2 innate lymphoid cells (ILC2) as well as B cells possibly mediated through the breakdown of the Fms-related tyrosine kinase 3 ligand (Flt3L)-mediated homeostatic feedback loop. Furthermore, the constitutive loss of cDCs accelerates skin colonization of Staphylococcus aureus (S. aureus), that associated with disease flare. Thus, cDCs maintains immune homeostasis to prevent the occurrence of immune abnormalities to maintain the functional skin barrier for mitigating AD flare.
DOI： 10.3389/fimmu.2021.712676
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Depletion of HMGB2 causes seminiferous tubule atrophy via aberrant expression of androgen and estrogen receptors in mouse testis. 査読あり
Sugita N, Choijookhuu N, Yano K, Lee D, Ikenoue M, Fidya, Taniguchi N, Chosa E, Hishikawa Y.
Biology of Reproduction 2021年
担当区分：最終著者, 責任著者 掲載種別：研究論文（学術雑誌）
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黒毛和種経産牛の正常分娩に伴う子宮頸管熟化におけるコラーゲン組成に関連した変化
山之口 瑛悟, 北原 豪, 小林 郁雄, 邉見 広一郎, 菱川 善隆, CHOIJOOKHUU Narantsog, 山口 良二, 大澤 健司
日本繁殖生物学会 講演要旨集 114 ( 0 ) OR-32 - OR-32 2021年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：公益社団法人 日本繁殖生物学会
【目的】分娩に伴う頸管熟化には生理的な炎症反応を伴うこと，さらにⅠ型コラーゲンの変化が頸管熟化に関連することがヒトやマウスでは示唆されているが，牛では不明である。牛の臨床現場では長期在胎や陣痛微弱による難産と死産が問題となっており，このような問題を防ぐために頸管熟化を促進させる方法の開発と応用が期待される。そこで，本研究では牛における正常な子宮頸管熟化機構と関連する変化の一端を明らかにすることを目的として，妊娠後期から分娩までのコラーゲンの変化に注目した試験を実施した。【材料と方法】宮崎大学農学部附属牧場の2～14産目の黒毛和種経産牛14頭を供試した。人工授精から分娩までの日数は293±4（平均±SD）日であった。人工授精後200（±3）日，260（±3）日，274（±3）日，288（±3）日，以降7日間隔で分娩直前（0～6日前）まで子宮頸管組織をパンチ生検で採取，さらに子宮頸管粘液を用手で採取した。頸管組織はピクロシリウスレッド染色し，偏光顕微鏡で観察と撮影を行い，得られた画像を用いⅠ型コラーゲンを示す領域が組織の総面積に占める割合を画像処理ソフト（ImageJ）で算出した。頸管粘液はディフクイック染色で有核細胞400個に対する多形核好中球の割合（PMN％）を算出した。【結果】Ⅰ型コラーゲンの組織に対する割合は，初回採材（分娩の12～13週間前）時点で94.8%から最終採材時では72.5％と低下した（p<0.05）。頸管粘液中のPMN％は初回採材時に最も低く（0.01％），分娩4～5週間前までに22.0％と上昇（p<0.05）し，分娩1週間前までに最高値（50.9％）を示した。【考察】以上の結果より，牛の頸管熟化には頸管組織におけるⅠ型コラーゲンの減少が関与していることが示唆された。また，頸管粘液中のPMNの増加の後にコラーゲンが変化し始めていることから，PMNによる炎症とPMNが分泌するコラゲナーゼが頸管熟化に影響することが推察された。
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Miyanaga N., Takagi H., Uto T., Fukaya T., Nasu J., Fukui T., Nishikawa Y., Sparwasser T., Choijookhuu N., Hishikawa Y., Nakamura T., Tono T., Sato K.
Communications Biology 3 ( 1 ) 742 2020年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Communications Biology
While sublingual immunotherapy (SLIT) is known as an allergen-specific treatment for type-1 allergies, how it controls allergic pathogenesis remains unclear. Here, we show the prerequisite role of conventional dendritic cells in submandibular lymph nodes (ManLNs) in the effectiveness of SLIT for the treatment of allergic disorders in mice. Deficiency of conventional dendritic cells or CD4+Foxp3+ regulatory T (Treg) cells abrogates the protective effect of SLIT against allergic disorders. Furthermore, sublingual antigenic application primarily induces antigen-specific CD4+Foxp3+ Treg cells in draining ManLNs, in which it is severely impaired in the absence of cDCs. In ManLNs, migratory CD11b+ cDCs are superior to other conventional dendritic cell subsets for the generation of antigen-specific CD4+Foxp3+ Treg cells, which is reflected by their dominancy in the tolerogenic features to favor this program. Thus, ManLNs are privileged sites in triggering mucosal tolerance mediating protect effect of SLIT on allergic disorders that requires a tolerogenesis of migratory CD11b+ conventional dendritic cells.
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Miyanaga N, Takagi H, Uto T, Fukaya T, Nasu J, Fukui T, Nishikawa Y, Sparwasser T, Choijookhuu N, Hishikawa Y, Nakamura T, Tono T, and Sato K
Communications Biology 2020年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Mai NNH, Yamaguchi Y, Choijookhuu N, Matsumoto J, Nanashima A, Takagi H, Sato K, Tuan LQ, Hishikawa Y.
Acta Histochemica et Cytochemica 53 ( 4 ) 61 - 72 2020年9月
担当区分：最終著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Acta Histochemica et Cytochemica
Photodynamic therapy (PDT) uses photosensitizer activation by light of a specific wavelength, and is a promising treatment for various cancers; however, the detailed mechanism of PDT remains unclear. Therefore, we investigated the anticancer effect of PDT using a novel phosphorus tetraphenylporphyrin (Ptpp) in combination with light emitting diodes (Ptpp-PDT) in the NOZ human biliary cancer cell line. Cell viability and apoptosis were examined by MTT assay, flow cytometry and TUNEL assay for 24 hr after Ptpp-PDT. MitoTracker and JC-1 were used as markers of mitochondrial localization and membrane potential. The levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes, Bcl-2 family proteins, cytochrome c and cleaved caspase-3 were examined by western blotting and immunohistochemistry. The results revealed that Ptpp localized to mitochondria, and that Ptpp-PDT efficiently decreased cell viability in a dose-and time-dependent manner. JC-1 and OXPHOS complexes decreased, but apoptotic cells increased from 6 to 24 hr after Ptpp-PDT. A decrease in Bcl-xL and increases in Bax, cytochrome c and cleaved caspase-3 were also found from 6 to 24 hr after Ptpp-PDT. Based on these results, we conclude that Ptpp-PDT induces anticancer effects via the mitochondrial apoptotic pathway by altering the Bax/Bcl-xL ratio, and could be an effective treatment for human biliary cancer.
DOI： 10.1267/ahc.20-00002
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Pivotal Role of CD103 in the Development of Psoriasiform Dermatitis 査読あり
Fukui T, Fukaya T, Uto T, Takagi H, Nasu J, Miyanaga N, Nishikawa Y, Koseki H, Choijookhuu N, Hishikawa Y, Yamashita Y, Sato K.
Scientific Reports 10 ( 1 ) 8371 2020年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
The integrin αE known as CD103 binds integrin β7 to form the complete heterodimeric integrin molecule αEβ7. CD103 is mainly expressed by lymphocytes within epithelial tissues of intestine, lung, and skin as well as subsets of mucosal and dermal conventional dendritic cells (cDCs). CD103 has been originally implicated in the attachment of lymphocytes to epithelium in the gut and skin through the interaction with E-cadherin expressed on intestinal epithelial cells, keratinocytes, and Langerhans cells (LCs). However, an impact of CD103 on the cutaneous immune responses and the development of inflammatory skin diseases remains elusive. Here, we report that CD103 regulates the development of psoriasiform dermatitis through the control of the function of cDCs. Deficiency in CD103 exacerbates psoriasiform dermatitis, accompanied by excessive epidermal hyperplasia and infiltration of inflammatory leukocytes. Furthermore, deficiency in CD103 not only accelerates the production of proinflammatory cytokines in psoriatic lesions but also promotes the generation of lymphocytes producing interleukin (IL)-17 in the skin-draining peripheral lymph nodes (PLNs). Under the deficiency in CD103, cDCs localized in PLNs enhance cytokine production following activation. Thus, our findings reveal a pivotal role for CD103 in the control of the function of cDCs to regulate cutaneous inflammation in psoriasiform dermatitis.
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Diep NV, Choijookhuu N, Fuke N, Myint O, Izzati UZ, Suwanruengsri M, Hishikawa Y, Yamaguchi R
Transboundary and Emerging Diseases 67 ( 6 ) 2589 - 2601 2020年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Transboundary and Emerging Diseases
We previously reported the coinfection of novel porcine epidemic diarrhoea virus (PEDV) variants bearing large deletions in the S protein and PEDVs possessing an intact S protein (S-intact PEDV) in domestic pigs in Japan. The variants were frequently observed in pig farms with persistent or recurrent infection. To elucidate the role of the variants in persistent infections and their tropism properties, we genetically characterized and immunohistochemically detected PEDVs collected in primary and recurrent outbreaks in two persistently infected farms. Our results revealed coinfection of the PEDV variants bearing a 214-amino acid deletion in the S protein and S-intact PEDVs in the lungs of the naturally infected pigs. New tropisms of PEDV, including epithelial cells and submucosal glands of the airway tract, epithelial cells of the bile duct, and monocytes/macrophages were identified. The findings elucidate the mechanism of PEDV infection, epidemiology and pattern changes in the disease.
DOI： 10.1111/tbed.13607
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Abnormal development of zebrafish after knockout and knockdown of ribosomal protein L10a 査読あり
Palasin, K., Uechi, T., Yoshihama, M., Srisowanna, N., Choijookhuu, N., Hishikawa, Y., Kenmochi, N., Chotigeat, W.
Scientific Reports 2019年12月
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The effect of estrogen on hepatic fat accumulation during early phase of liver regeneration after partial hepatectomy in rats 査読あり
Srisowanna N, Choijookhuu N, Yano K, Batmunkh B, Ikenoue M, Mai NNH, Yamaguchi Y and Hishikawa Y.
Acta Histochemica et Cytochemica 52 ( 4 ) 1 - 9 2019年9月
担当区分：最終著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1267/ahc.19018
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Contamination of arsenic in drinking water in Ayeyarwady delta region, Myanmar. 査読あり
Phyu KP, Zin PW, Aung MN, Lar MM, Hishikawa Y, Maruyama M, Yokota H, Thant KZ, Wai KT, Yano Y
World Journal of Pharmaceutical and Life Sciences 5 ( 8 ) 42 - 48 2019年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Peripheral neuropathy induced by drinking water contaminated with low-dose arsenic in Myanmar. 査読あり
Mochizuki, H. Phyu, K. P. Aung, M. N. Zin, P. W. Yano, Y. Myint, M. Z. Thit, W. M. Yamamoto, Y. Hishikawa, Y. Thant, K. Z. Maruyama, M. Kuroda, Y.
Environmental Health and Preventive Medicine 2019年4月
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Kyaw MNH*, Yamaguchi Y* (equally contributed), Choijookhuu N, Yano K, Takagi H, Takahashi N, Oo PS, Sato K, Hishikawa Y
Acta Histochemica et Cytochemica 52 ( 1 ) 1 - 8 2019年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：日本組織細胞化学会
Hepatoid adenocarcinoma (HAC) is a rare and aggressive gastrointestinal tract cancer that is characterized by hepatic differentiation and production of alpha-fetoprotein (AFP). Cisplatin is mainly used to treat HAC, but the efficacy is poor. Recently, the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), was approved as an anticancer agent. In this study, we investigated the anticancer effect of SAHA in combination with cisplatin in VAT-39 cells, a newly established HAC cell line. Cell viability and apoptosis were examined by MTT assay, flow cytometry and TUNEL assay. Expression of H3S10, cleaved caspase-3, Bax, and Bcl-2 were evaluated by immunohistochemistry and western blotting. AFP levels were examined in VAT-39 cells and culture medium. Combined treatment with cisplatin and SAHA efficiently inhibited cell proliferation and decreased cell viability. Apoptotic cells, but not necrotic cells, were significantly increased following the combined treatment, and an increase in the Bax/Bcl-2 ratio indicated that the combination of cisplatin and SAHA induced apoptosis through the mitochondrial pathway. VAT-39 cells treated with cisplatin and SAHA also partially lost their main characteristic of AFP production. We conclude that cisplatin and SAHA have a synergistic anticancer effect of inducing apoptosis, and that this combination treatment may be effective for HAC.
DOI： 10.1267/ahc.18044
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Fukaya T., Fukui T., Uto T., Takagi H., Nasu J., Miyanaga N., Arimura K., Nakamura T., Koseki H., Choijookhuu N., Hishikawa Y., Sato K.
Frontiers in Immunology 9 ( JUN ) 1418 2018年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Frontiers in Immunology
© 2018 Fukaya, Fukui, Uto, Takagi, Nasu, Miyanaga, Arimura, Nakamura, Koseki, Choijookhuu, Hishikawa and Sato. Disruption of skin homeostasis can lead to inflammatory cutaneous diseases resulting from the dysregulated interplay between epithelial keratinocytes and immune cells. Interleukin (IL)-22 signaling through membrane-bound IL-22 receptor 1 (IL-22R1) is crucial to maintain cutaneous epithelial integrity, and its malfunction mediates deleterious skin inflammation. While IL-22 binding protein (IL-22BP) binds IL-22 to suppress IL-22 signaling, how IL-22BP controls epithelial functionality to prevent skin inflammation remains unclear. Here, we describe the pivotal role of IL-22BP in mediating epithelial autoregulation of IL-22 signaling for the control of cutaneous pathogenesis. Unlike prominent expression of IL-22BP in dendritic cells in lymphoid tissues, epidermal keratinocytes predominantly expressed IL-22BP in the skin in the steady state, whereas its expression decreased during the development of psoriatic inflammation. Deficiency in IL-22BP aggravates psoriasiform dermatitis, accompanied by abnormal hyperproliferation of keratinocytes and excessive cutaneous inflammation as well as enhanced dermal infiltration of granulocytes and γδT cells. Furthermore, IL-22BP abrogates the functional alternations of keratinocytes upon stimulation with IL-22. On the other hand, treatment with IL-22BP alleviates the severity of cutaneous pathology and inflammation in psoriatic mice. Thus, the fine-tuning of IL-22 signaling through autocrine IL-22BP production in keratinocytes is instrumental in the maintenance of skin homeostasis.
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Critical role of plasmacytoid dendritic cells in induction of oral tolerance. 査読あり
Uto T., Takagi H., Fukaya T., Nasu J., Fukui T., Miyanaga N., Arimura K., Nakamura T., Choijookhuu N., Hishikawa Y., Sato K.
Journal of Allergy and Clinical Immunology. 141 ( 6 ) 2156 - 2167 2018年6月
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HMGB2 is a novel adipogenic factor that regulates ectopic fat infiltration in skeletal muscles 査読あり
Lee D, Taniguchi N, Sato K, Choijookhuu N, Hishikawa Y, Kataoka H, Morinaga H, Lotz M, Chosa E
Scientific Reports 8 ( 1 ) 9601 2018年6月
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Estrogen Regulates Mitochondrial Morphology through Phosphorylation of Dynamin-related Protein 1 in MCF7 Human Breast Cancer Cells 査読あり
Oo PS, Yamaguchi Y, Sawaguchi A, Kyaw MNH, Choijookhuu N, Ali MN, Srisowanna N, Hino SI, Hishikawa Y
Acta Histochemica et Cytochemica 51 ( 1 ) 21 - 31 2018年3月
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The HDAC Inhibitor, SAHA, Prevents Colonic Inflammation by Suppressing Pro-inflammatory Cytokines and Chemokines in DSS-induced Colitis. 査読あり
Ali MN, Choijookhuu N, Takagi H, Srisowanna N, Nguyen Nhat Huynh M, Yamaguchi Y, Synn Oo P, Tin Htwe Kyaw M, Sato K, Yamaguchi R, Hishikawa Y
Acta Histochemica et Cytochemica 51 ( 1 ) 33 - 40 2018年3月
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Photodynamic therapy of human biliary cancer cell line using combination of phosphorus porphyrins and light emitting diode 査読あり
Matsumoto J., Suzuki K., Yasuda M., Yamaguchi Y., Hishikawa Y., Imamura N., Nanashima A.
Bioorganic & Medicinal Chemistry. 25 ( 24 ) 6536 - 6541 2017年12月
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Novel role of Rac-Mid1 signaling in medial cerebellar development 査読あり
Nakamura T, Ueyama T, Ninoyu Y, Sakaguchi H, Choijookhuu N, Hishikawa Y, Kiyonari H, Kohta M, Sakahara M, de Curtis I, Kohmura E, Hisa Y, Aiba A, Saito N
Development (Cambridge, England) 144 ( 10 ) 1863 - 1875 2017年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1242/dev.147900
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Flexible adaptation of male germ cells from female iPSCs of endangered Tokudaia osimensis. 査読あり
Honda A, Choijookhuu N, Izu H, Kawano Y, Inokuchi M, Honsho K, Lee AR, Nabekura H, Ohta H, Tsukiyama T, Ohinata Y, Kuroiwa A, Hishikawa Y, Saitou M, Jogahara T, Koshimoto C.
Science advances 3 ( 5 ) e1602179 2017年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Discrimination of Stem Cell Status after Subjecting Cynomolgus Monkey Pluripotent Stem Cells to Naïve Conversion. 査読あり
Honda A, Kawano Y, Izu H, Choijookhuu N, Honsho K, Nakamura T, Yabuta Y, Yamamoto T, Takashima Y, Hirose M, Sankai T, Hishikawa Y, Ogura A, Saitou M.
Sci Rep. 7 45285 2017年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1038/srep45285
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Estrogen accelerates cell proliferation through estrogen receptor alpha during rat liver regeneration after partial hepatectomy. 査読あり
Baatarsuren Batmunkh, Narantsog Choijookhuu, Naparee Srisowanna, Uugantsetseg Byambatsogt, Phyu Synn Oo, Mohmand Noor Ali, Yuya Yamaguchi, Yoshitaka Hishikawa
Acta Histochem. Cytochem 50 ( 1 ) 39 - 48 2017年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Frequency of CD4+CD161+ T cell and interleukin-10 expression in inflammatory bowel diseases. 査読あり
Kazuyo Tsuchiya, Takuto Ikeda, Baatarsuren Batmunkh, Narantsog Choijookhuu, Hidenobu Ishizaki, Masayuki Hotokezaka, Yoshitaka Hishikawa and Atsushi Nanashima
Acta Histochem. Cytochem 50 ( 1 ) 21 - 28 2017年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Arsenic trioxide induces ROS activity and DNA damage, leading to G0/G1 extension in skin fibroblasts through the ATM-ATR-associated Chk pathway. 査読あり
Jutapon Chayapong, Harishkumar Madhyastha,Radha Madhyastha,Queen Intan Nurrahmah,Yuichi Nakajima,Narantsog Choijookhuu,Yoshitaka Hishikawa,Masugi Maruyama
Environ Sci Pollut Res Int. 24 ( 6 ) 5316 - 5325 2017年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Crucial role of plasmacytoid dendritic cells in the development of acute colitis through the regulation of intestinal inflammation Mucosal Immunol. 査読あり
K Arimura, H Takagi, T Uto, T Fukaya, T Nakamura, N Choijookhuu, Y Hishikawa, Y Yamashita and K Sato
Mucosal Immunol 10 ( 4 ) 957 - 970 2016年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1038/mi.2016.96
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Plasmacytoid dendritic cells orchestrate TLR7-mediated innate and adaptive immunity for the initiation of autoimmune inflammation. 査読あり
Takagi H, Arimura K, Uto T, Fukaya T, Nakamura T, Choijookhuu N, Hishikawa Y, Sato K.
Scientific Reports 6 1 - 18 2016年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1038/srep24477
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The role of estrogen receptors in intestinal homeostasis and disease 査読あり
Choijookhuu N, Hino SI, Oo PS, Batmunkh B, Hishikawa Y
Receptors Clin Investig 3 ( 1 ) 2016年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.14800/rci.1109
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Hyperbaric Oxygen Therapy Suppresses Apoptosis and Promotes Renal Tubular Regeneration After Renal Ischemia/Reperfusion Injury in Rats. 査読あり
Heihachi Migita, Shigenori Yoshitake,Yoshihiro Tange,Narantsog Choijookhuu,andYoshitaka Hishikawa
Nephro-Urology Monthly (International Bimonthy Medical Journal) 8 ( 1 ) e34421 2016年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Arsenic acid inhibits proliferation of skin fibroblasts, and increases cellular senescence through ROS mediated MST1-FOXO signaling pathway. 査読あり
Yamaguchi Y, Madhyastha H, Madhyastha R, Choijookhuu N, Hishikawa Y, Pengjam Y, Nakajima Y, Maruyama M
J Toxicol Sci. 41 ( 1 ) 105 - 113 2016年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.2131/jts.41.105
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Transplanted fibroblast cell sheets promote migration of hepatic progenitor cells in the incised host liver in allogenic rat model. 査読あり
Muraoka I, Takatsuki M, Sakai Y, Tomonaga T, Soyama A, Hidaka M, Hishikawa Y, Koji T, Utoh R, Ohashi K, Okano T, Kanematsu T, Eguchi S
J Tissue Eng Regen Med 11 E108 - E115 2015年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1002/term.1718.
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Ontogenetic changes in the expression of estrogen receptor β in mouse duodenal epithelium.（共著） 査読あり
Choijookhuu N, Hino SI, Oo PS, Batmunkh B, Ali MN, Kyaw MTH, Hishikawa Y
Clinics and research in hepatology and gastroenterology 39 ( 4 ) 499 - 507 2015年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Maintenance of stereocilia and apical junctional complexes by Cdc42 in cochlear hair cells 査読あり
Ueyama T, Sakaguchi H, Nakamura T, Goto A, Morioka S, Shimizu A, Nakao K, Hishikawa Y, Ninoyu Y, Kassai H, Suetsugu S, Koji T, Fritzsch B, Yonemura S, Hisa Y, Matsuda M, Aiba A, Saito N
JOURNAL OF CELL SCIENCE 127 ( 8 ) 2040 - 2052 2014年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1242/?jcs.143602
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Coexpression of Ang1 and Tie2 in Odontoblasts of Mouse Developing and Mature Teeth-A New Insight into Dentinogenesis 査読あり
Nakajima K, Shibata Y, Hishikawa Y, Suematsu T, Mori M, Fukuhara S, Koji T, Sawase T, Ikeda T
Acta Histochem. Cytochem. 47 ( 1 ) 19 - 25 2014年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1267/ahc.13043
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Accelerated proliferation of hepatocytes in rats with iron overload after partial hepatectomy. 査読あり
An S, Soe K, Akamatsu M, Hishikawa Y, Koji T,
Histochemistry and Cell Biology 138 ( 5 ) 773 - 786 2012年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Estrogen-dependent regulation of sodium/hydrogen exchanger-3 (NHE3) expression via estrogen receptor β in proximal colon of pregnant mice. 査読あり
Choijookhuu N, Sato Y, Nishino T, Endo D, Hishikawa Y, Koji T
Histochem Cell Biol 137 575 - 587 2012年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Epigallocatechin gallate suppresses peritoneal fibrosis in mice. Chemico-Biological Interactions. 査読あり
Kitamura M, Nishino T, Obata Y, Furusu A, Hishikawa Y, Koji T, Kohno S,
Chemico-Biological Interactions 195 ( 1 ) 95 - 104 2012年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1016/j.cbi.
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Immunohistochemical analysis of histone H3 modifications in germ cells during mouse spermatogenesis. "jointly worked" 査読あり
Song N, Liu J, An S, Nishino T, Hishikawa Y, Koji T.
Acta Histochem. Cytochem. 44 183 - 190 2011年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Expression of keratinocyte growth factor and its receptor in noncholesteatomatous and cholesteatomatous chronic otitis media. "jointly worked" 査読あり
Yamamoto-Fukuda T, Takahashi H, Terakado M, Hishikawa Y, Koji T.
Otol. Neurotol. 31 745 - 751 2010年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Aberrant expression of interferon regulatory factor 3 in human lung cancer. "jointly worked" 査読あり
Tokunaga T, Naruke Y, Shigematsu S, Kohno T, Yasui K, Ma Y, Chua KJ, Katayama I, Nakamura T, Hishikawa Y, Koji T, Yatabe Y, Nagayasu T, Fujita T, Matsuyama T, Hayashi H.
Biochem. Biophys. Res. Commun. 397 202 - 207 2010年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Expression of keratinocyte growth factor and its receptor in rat tracheal cartilage: Possible involvement in wound healing of the damaged cartilage. "jointly worked" 査読あり
Abo T, Nagayasu T, Hishikawa Y, Tagawa T, Nanashima A, Yamayoshi T, Matsumoto K, An S, Koji T.
Acta Histochem. Cytochem. 43 89 - 98 2010年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Pathogenesis of middle ear cholesteatoma; a new model of experimentally induced cholesteatoma in mongolian gerbils. "jointly worked" 査読あり
Yamamoto-Fukuda T, Hishikawa Y, Shibata Y, Kobayashi T, Takahashi H, Koji T.
Am. J. Pathol. 176 2602 - 2606 2010年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Localization of HSP47 mRNA in murine bleomycin-induced pulmonary fibrosis. "jointly worked" 査読あり
Kakugawa T, Mukae H, Hishikawa Y, Ishii H, Sakamoto N, Ishimatsu Y, Fujii T, Koji T, Kohno S.
Virchows Archiv. 456 309 - 315 2010年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Human papillomavirus infection and its possible correlation with p63 expression in cervical cancer in Japan, Mongolia, and Myanmar. "jointly worked" 査読あり
Shirendeb U, Hishikawa Y, Moriyama S, Win N, Thu MMM, Mar KS, Khatanbaatar G, Masuzaki H, Koji T.
Acta Histochem. Cytochem. 42 181 - 190 2009年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Keratinocyte growth factor accelerates compensatory growth in the remaining lung after trilobectomy in rats. "jointly worked" 査読あり
Matsumoto K, Nagayasu T, Hishikawa Y, Tagawa T, Yamayoshi T, Abo T, Tobinaga S, Furukawa K, Koji T.
J. Thorac. Cardiovasc. Surg. 137 1499 - 1507 2009年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Improvement of in situ PCR by optimization of PCR cycle number and proteinase K concentration: Localization of X chromosome-linked phosphoglycerate kinase-1 gene in mouse reproductive organs. "jointly worked" 査読あり
Hishikawa Y, An S, Yamamoto-Fukuda T, Shibata Y, Koji T.
Acta Histochem. Cytochem. 42 15 - 21 2009年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Adhesion-dependent growth of primary adult T cell leukemia cells with down-regulation of HTLV-1 p40Tax protein: a novel in vitro model of the growth of acute ATL cells. "jointly worked" 査読あり
Nagai K, Jinnai I, Hata T, Usui T, Sasaki D, Tsukasaki K, Sugahara K, Hishikawa Y, Yamada Y, Tanaka Y, Koji T, Mano H, Kamihira S, Tomonaga M.
Int. J. Hematol. 88 551 - 564 2008年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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In situ detection of methylated DNA by histo endonuclease-linked detection of methylated DNA sites: a new principle of analysis of DNA methylation. "jointly worked" 査読あり
Koji T, Kondo S, Hishikawa Y, An S, Sato Y.
Histochem. Cell Biol. 130 917 - 925 2008年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Topical application of 5-fluorouracil on attic cholesteatoma results in downregulation of keratinocyte growth factor and reduction of proliferative activity. "jointly worked" 査読あり
Yamamoto-Fukuda T, Terakado M, Hishikawa Y, Koji T, Takahashi H.
Eur. Arch. Otorhinolaryngol. 265 1173 - 1178 2008年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation. "jointly worked" 査読あり
Nakagawa T, Kajitani T, Togo S, Masuko N, Ohdan H, Hishikawa Y, Koji T, Matsuyama T, Ikura T, Muramatsu M, Ito T.
Gene Dev. 22 37 - 49 2008年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Lung injury after ischemia-reperfusion of small intestine in rats involves apoptosis of type II alveolar epithelial cells mediated by TNF-α and activation of Bid pathway. "jointly worked" 査読あり
An S, Hishikawa Y, Liu J, Koji T.
Apoptosis 12 1989 - 2001 2007年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Enhanced osseointegration by the chemotactic activity of plasma fibronectin for cellular fibronectin positive cells. "jointly worked" 査読あり
Jimbo R, Sawase T, Shibata Y, Hirata K, Hishikawa Y, Tanaka Y, Bessho K, Ikeda T, Atsuta M.
Biomaterials 28 3469 - 3477 2007年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Immunohistochemical analysis of connexin43 expression in infertile human testes. "jointly worked" 査読あり
Matsuo Y, Nomata K, Eguchi J, Aoki D, Hayashi T, Hishikawa Y, Kanetake H, Shibata Y, Koji T.
Acta Histochem. Cytochem. 40 69 - 75 2007年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Possible protection of sinusoidal endothelial cells by endothelin B receptor during hepatic warm ischemia-reperfusion. "jointly worked" 査読あり
Mochizuki K, Ohno Y, Kanematsu T, Sakurai-Yamashita Y, Niwa M, Hishikawa Y, Koji T.
Surg. Today 37 460 - 467 2007年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Possible correlation between iron deposition and enhanced proliferating activity in hepatitis C virus-positive hepatocellular carcinoma in Myanmar (Burma). "jointly worked" 査読あり
Soe K, Hishikawa Y, Fukuzawa Y, Win N, Yin KS, Win KM, Myint AA, Koji T.
J. Gastroenterol. 42 225 - 235 2007年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Identification of estrogen receptor β-positive intraepithelial lymphocytes and their possible roles in normal and tubal pregnancy oviducts. "jointly worked" 査読あり
Ulziibat S, Ejima K, Shibata Y, Hishikawa Y, Kitajima M, Fujishita A, Ishimaru T, Koji T.
Hum. Reprod. 21 2281 - 2289 2006年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Diethylstilbestrol increases the density of prolactin cells in male mouse pituitary by inducing proliferation of prolactin cells and transdifferentiation of gonadotropic cells. "jointly worked" 査読あり
Shukuwa K, Izumi S, Hishikawa Y, Ejima K, Inoue S, Muramatsu M, Ouchi Y, Kitaoka T, Koji T.
Histochem. Cell Biol. 126 111 - 123 2006年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Expression of the Snurf-Snrpn IC transcript in the oocyte and its putative role in the imprinting establishment of the mouse 7C imprinting domain. "jointly worked" 査読あり
Mapendano CK, Kishino T, Miyazaki K, Kondo S, Yoshiura K, Hishikawa Y, Koji T, Niikawa N, Ohta T.
J. Hum. Genet. 51 236 - 243 2006年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Enhanced expression of insulin-like growth factor-binding proteins in human osteoarthritic cartilage detected by immunohistochemistry and in situ hybridization. "jointly worked" 査読あり
Iwanaga H, Matsumoto T, Enomoto H, Okano K, Hishikawa Y, Shindo H, Koji T.
Osteoarthr. Cartilage 13 439 - 448 2005年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Induction of cell death in rat small intestine by ischemia reperfusion: differential roles of Fas/Fas ligand and Bcl-2/Bax systems depending upon cell types. "jointly worked" 査読あり
An S, Hishikawa Y, Koji T.
Histochem. Cell Biol. 123 249 - 261 2005年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Overexpression of macrophage migration inhibitory factor induces angiogenesis and deteriorates prognosis after radical resection for hepatocellular carcinoma. "jointly worked" 査読あり
Hira E, Ono T, Dhar DK, El-Assal ON, Hishikawa Y, Yamanoi A, Nagasue N.
Cancer 103 588 - 598 2005年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Pranlukast, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from leukotriene receptor antagonism. "jointly worked" 査読あり
Fukushima C, Matsuse H, Hishikawa Y, Kondo Y, Machida I, Saeki S, Kawano T, Tomari S, Obase Y, Shimoda T, Koji T, Kohno S.
Int. Arch. Allergy Immunol. 136 165 - 172 2005年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Apoptosis and its pathway in early post-implantation embryos of diabetic rats. "jointly worked" 査読あり
Sun F, Kawasaki E, Akazawa S, Hishikawa Y, Sugahara K, Kamihira S, Koji T, Eguchi K.
Diabetes Res. Clin. Pract. 67 110 - 118 2005年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Early human preantral follicles have relaxin and relaxin receptor (LGR7), and relaxin promotes their development. "jointly worked" 査読あり
Shirota K, Tateishi K, Koji T, Hishikawa Y, Hachisuga T, Kuroki M, Kawarabayashi T.
J. Clin. Endocrinol. Metab. 90 516 - 521 2005年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Expression of keratinocyte growth factor and its receptor in human breast cancer: its inhibitory role in the induction of apoptosis possibly through the overexpression of Bcl-2. "jointly worked" 査読あり
Hishikawa Y, Tamaru N, Ejima K, Hayashi T, Koji T.
Arch. Histol. Cytol. 67 455 - 464 2004年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Estrogen receptor-associated expression of keratinocyte growth factor and its possible role in the inhibition of apoptosis in human breast cancer. "jointly worked" 査読あり
Tamaru N, Hishikawa Y, Ejima K, Nagasue N, Inoue S, Muramatsu M, Hayashi T, Koji T.
Lab. Invest. 84 1460 - 1471 2004年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Coexpression of keratinocyte growth factor and its receptor in normal and prostate cancer tissues: possible formation of autonomous andromedin loop. "jointly worked" 査読あり
Aoki D, Yamamoto-Fukuda T, Hishikawa Y, Nakamura M, Sakai H, Kanetake H, Koji T.
Acta Histochem. Cytochem. 37 379 - 389 2004年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Expression of keratinocyte growth factor/fibroblast growth factor-7 and its receptor in human lung cancer: correlation with tumour proliferative activity and patient prognosis. "jointly worked" 査読あり
Yamayoshi T, Nagayasu T, Matsumoto K, Abo T, Hishikawa Y, Koji T.
J. Pathol. 204 110 - 118 2004年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Identification and localization of estrogen receptor α- and β-positive cells in adult male and female mouse intestine at various estrogen levels. "jointly worked" 査読あり
Kawano N, Koji T, Hishikawa Y, Murase K, Murata I, Kohno S.
Histochem. Cell Biol. 121 399 - 405 2004年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Complement C4b-binding protein as a novel murine epididymal secretory protein. "jointly worked" 査読あり
Nonaka MI, Hishikawa Y, Moriyama N, Koji T, Ogata RT, Kudo A, Kawakami H, Nonaka M.
Biol. Reprod. 69 1931 - 1939 2003年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Transforming growth factor-β 1 released from the spleen exerts a growth inhibitory effect on liver regeneration in rats. "jointly worked" 査読あり
Ueda S, Yamanoi A, Hishikawa Y, Dhar DK, Tachibana M, Nagasue N.
Lab. Invest. 83 1595 - 1603 2003年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Expression of tumor-associated membrane antigen, RCAS1, in human colorectal carcinomas and possible role in apoptosis of tumor-infiltrating lymphocytes. "jointly worked" 査読あり
Okada K, Nakashima M, Komuta K, Hashimoto S, Okudaira S, Baba N, Hishikawa Y, Koji T, Kanematsu T, Watanabe T.
Mod. Path. 16 679 - 685 2003年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Zone-dependent expression of estrogen receptors α and β in human benign prostatic hyperplasia. "jointly worked" 査読あり
Tsurusaki T, Aoki D, Kanetake H, Inoue S, Muramatsu M, Hishikawa Y, Koji T.
J. Clin. Endocrinol. Metab. 88 1333 - 1340 2003年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Expression of the c-Met proto-oncogene and its possible involvement in liver invasion in adult T-cell leukemia. "jointly worked" 査読あり
Imaizumi Y, Murota H, Kanda S, Hishikawa Y, Koji T, Taguchi T, Tanaka Y, Yamada Y, Ikeda S, Kohno T, Yamamoto K, Mori N, Tomonaga M, Matsuyama T.
Clin. Cancer Res. 9 181 - 187 2003年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Possible involvement of keratinocyte growth factor and its receptor in enhanced epithelial-cell proliferation and acquired recurrence of middle-ear cholesteatoma. "jointly worked" 査読あり
Yamamoto-Fukuda T, Aoki D, Hishikawa Y, Kobayashi T, Takahashi H, Koji T.
Lab. Invest. 83 123 - 136 2003年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Diethylstilbestrol attenuates antioxidant activities in testis from male mice. "jointly worked" 査読あり
Kondo T, Goto S, Ihara Y, Urata Y, Ikeda S, Hishikawa Y, Izumi S, Shin M, Koji T.
Free Radic. Res. 36 957 - 966 2002年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Involvement of Bax redistribution in the induction of germ cell apoptosis in neonatal mouse testes. "jointly worked" 査読あり
Damavandi E, Hishikawa Y, Izumi S, Shin M, Koji T.
Acta Histochem. Cytochem. 35 449 - 459 2002年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Involvement of Fas/Fas ligand in the induction of apoptosis in chronic sialadenitis of minor salivary glands including Sjögren's Syndrome. "jointly worked" 査読あり
Shibata Y, Hishikawa Y, Izumi S, Fujita S, Yamaguchi A, Koji T.
Hum. Cell 15 52 - 60 2002年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Immunoelectron microscopic identification of tRNA on ribosome particles in rat liver and placenta. "jointly worked" 査読あり
Izumi S, Shin M, Hishikawa Y, Koji T.
J. Electr. Microsc. Technol. Med. Biol. 15 72 - 75 2001年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Partial tolerance of subcutaneously transplanted xenogeneic tumour cell graft by Fas-mediated immunosuppression. "jointly worked" 査読あり
Sawada T, Koji T, Hishikawa Y, Kishimoto K, Nagayasu T, Takahashi T, Oka T, Ayabe H.
Immunology 103 81 - 89 2001年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Expression of Fas and Fas ligand in normal and ischemia-reperfusion testes: involvement of the Fas system in the induction of germ cell apoptosis in the damaged mouse testis. "jointly worked" 査読あり
Koji T, Hishikawa Y, Ando H, Nakanishi Y, Kobayashi N.
Biol. Reprod. 64 946 - 954 2001年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Expression of metallothionein in colorectal cancers and synchronous liver metastases. "jointly worked" 査読あり
Hishikawa Y, Kohno H, Ueda S, Kimoto T, Dhar DK, Kubota H, Tachibana M, Koji T, Nagasue N.
Oncology 61 162 - 167 2001年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Effects of various decalcification protocols on detection of DNA strand breaks by terminal dUTP nick end labelling. "jointly worked" 査読あり
Yamamoto-Fukuda T, Shibata Y, Hishikawa Y, Shin M, Yamaguchi A, Kobayashi T, Koji T.
Histochem. J. 32 697 - 702 2000年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Concurrent expressions of metallothionein, glutathione-S-transferase-π and P-glycoprotein in colorectal cancers. "jointly worked" 査読あり
Sutoh I, Kohno H, Nakashima Y, Hishikawa Y, Tabara H, Tachibana M, Kubota H, Nagasue N.
Dis. Colon Rectum 43 221 - 232 2000年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Metallothionein expression correlates with metastatic and proliferative potential in squamous cell carcinoma of the oesophagus. "jointly worked" 査読あり
Hishikawa Y, Koji T, Dhar DK, Kinugasa S, Yamaguchi M, Nagasue N.
Br. J. Cancer 81 712 - 720 1999年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Prognostic significance of perioperative blood transfusions in resectable thoracic esophageal cancer. "jointly worked" 査読あり
Tachibana M, Tabara H, Kotoh T, Kinugasa S, Dhar DK, Hishikawa Y, Masunaga R, Kubota H, Nagasue N.
Am. J. Gastroenterol. 94 757 - 765 1999年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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The role of P-glycoprotein in human gastric cancer xenografts in response to chemotherapy. "jointly worked" 査読あり
Monden N, Abe S, Hishikawa Y, Yoshimura H, Kinugasa S, Dhar DK, Tachibana M, Nagasue N.
Int. J. Surg. Investig. 1 3 - 10 1999年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Overexpression of transforming growth factor-β1 in scirrhous carcinoma of the stomach correlates with decreased survival. "jointly worked" 査読あり
Kinugasa S, Abe S, Tachibana M, Hishikawa Y, Yoshimura H, Monden N, Dhar DK, Nagasue N.
Oncology 55 582 - 587 1998年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Prognostic significance of the expressions of metallothionein, glutathione-S-transferase-π, and P-glycoprotein in curatively resected gastric cancer. "jointly worked" 査読あり
Monden N, Abe S, Sutoh I, Hishikawa Y, Kinugasa S, Nagasue N.
Oncology 54 391 - 399 1997年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Overexpression of metallothionein correlates with chemoresistance to cisplatin and prognosis in esophageal cancer. "jointly worked" 査読あり
Hishikawa Y, Abe S, Kinugasa S, Yoshimura H, Monden N, Igarashi M, Tachibana M, Nagasue N.
Oncology 54 342 - 347 1997年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Growth kinetic study of human hepatocellular carcinoma using proliferating cell nuclear antigen and Lewis Y antigen: their correlation with transforming growth factor-α and β 1. "jointly worked" 査読あり
Yamaguchi M, Yu L, Hishikawa Y, Yamanoi A, Kubota H, Nagasue N.
Oncology 54 245 - 251 1997年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Prognostic significance of proliferating cell nuclear antigen (PCNA) in squamous cell carcinoma of the esophagus. "jointly worked" 査読あり
Kinugasa S, Tachibana M, Hishikawa Y, Abe S, Yoshimura H, Monden N, Dhar DK, Nagasue N.
Jpn. J. Clin. Oncol. 26 405 - 410 1996年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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食道アカラシアに合併した後天性全結腸hypoganglionosisの一例－酵素抗体法による免疫組織化学的検討－ 査読あり
菱川善隆, 五十嵐雅彦, 松尾 進, 中村輝久
日本小児外科学会雑誌 29 1273 - 1276 1993年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）