論文 - 菱川 善隆
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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