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Affiliation |
Faculty of Medicine School of Medicine Department of Anatomy, Histochemistry and Cell Biology |
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Assistant Professor |
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External Link |
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ISHIZUKA Takumi
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Research Areas 【 display / non-display 】
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Nanotechnology/Materials / Bio chemistry
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Nanotechnology/Materials / Chemical biology
Education 【 display / non-display 】
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The University of Tokyo Graduate School, Division of Engineering
- 2011.3
Country：Japan
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Tokyo Institute of Technology Faculty of Life Science and Engineering
- 2006.3
Country：Japan
Papers 【 display / non-display 】
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Lkham-Erdene B., Choijookhuu N., Kubota T., Uto T., Mitoma S., Shirouzu S., Ishizuka T., Kai K., Higuchi K., Aung K.M., Batmunkh J.E., Sato K., Hishikawa Y.
Acta Histochemica et Cytochemica 57 ( 5 ) 175 - 188 2024.10
Language：English Publishing type：Research paper (scientific journal) Publisher：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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HMGB2 Promotes De Novo Lipogenesis to Accelerate Hepatocyte Proliferation During Liver Regeneration Reviewed
Choijookhuu N., Yano K., Lkham-Erdene B., Shirouzu S., Kubota T., Fidya , Ishizuka T., Kai K., Chosa E., Hishikawa Y.
Journal of Histochemistry and Cytochemistry 72 ( 4 ) 245 - 264 2024.3
Language：English Publishing type：Research paper (scientific journal) Publisher：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.
Histochemistry and Cell Biology 161 ( 4 ) 325 - 336 2024.1
Language：English Publishing type：Research paper (scientific journal) Publisher：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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Protective role of estrogen through G-protein coupled receptor 30 in a colitis mouse model Reviewed
Fidya, Narantsog Choijookhuu, Makoto Ikenoue, Koichi Yano, Yu Yamaguma, Shinichiro Shirouzu, Kengo Kai, Takumi Ishizuka, Yoshitaka Hishikawa
Histochemistry and Cell Biology 161 ( 1 ) 81 - 93 2023.10
Language：English Publishing type：Research paper (scientific journal)
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Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility Reviewed
Shinichiro Shirouzu, Naohiro Sugita, Narantsog Choijookhuu, Yu Yamaguma, Kanako Takeguchi, Takumi Ishizuka, Mio Tanaka, Fidya, Kengo Kai, Etsuo Chosa, Yoshihiro Yamashita, Chihiro Koshimoto, Yoshitaka Hishikawa
Journal of Ovarian Research 15 ( 1 ) 133 - 133 2022.12
Language：English Publishing type：Research paper (scientific journal)
Books 【 display / non-display 】
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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in situ hybridization
石塚 匠，Narantsog Choijookhuu，柴田 恭明，小路 武彦，菱川 善隆（ Role： Joint author）
日本顕微鏡学会 2023.12
Language：Japanese Book type：Scholarly book
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In situ hybridization法
菱川 善隆, Narantsog Choijookhuu, 石塚 匠, 柴田 恭明, 小路 武彦（ Role： Joint author）
日本組織細胞化学会・中西印刷（株） 2022.7
Language：Japanese Book type：Scholarly book
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病理と臨床 2022年臨時増刊号(40巻): がんゲノム医療時代の分子腫瘍学
菱川 善隆, Narantsog Choijookhuu, 石塚 匠, 柴田 恭明, 小路 武彦（ Role： Joint author , 第1部 がんの分子病理学（序論）:FISH・ISH）
文光堂 2022.4
Language：Japanese Book type：Scholarly book
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G-Quadruplex Nucleic Acids
Takumi Ishizuka, Hong-Liang Bao, Yan Xu（ Role： Joint author , Chapter 26: 19F NMR Spectroscopy for the Analysis of DNA G-quadruplex Structures using 19F-labeled Nucleobase）
Springer 2019.8
Language：English Book type：Scholarly book
Presentations 【 display / non-display 】
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マウス精子形成過程におけるDNA四重鎖構造の発現動態
石塚 匠, Kham Mo Aung, Baljinnyam Lkham-Erdene, 久保田 壽樹, 甲斐 健吾, 菱川 善隆
第65回日本組織細胞化学会総会・学術集会 (群馬大学医学部) 2024.10.27
Event date： 2024.10.26 - 2024.10.27
Language：Japanese Presentation type：Oral presentation (general)
Venue：群馬大学医学部
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Dynamics of DNA G-quadruplex structures in mice Invited International conference
Takumi Ishizuka, Kham Mo Aung, Narantsog Choijookhuu, Koichi Yano, Shinichiro Shirouzu, Fidya, Makoto Ikenoue, Baljinnyam Lkham-Erdene, Toshiki Kubota, Kengo Kai, Yoshitaka Hishikawa
The 7th China-ASEAN Medical Education Series: Conference on the High-Quality Development and Innovation of Pharmaceutical Sciences (Guizhou Medical University) 2024.8.21
Event date： 2024.8.20 - 2024.8.22
Language：English Presentation type：Oral presentation (invited, special)
Venue：Guizhou Medical University Country：China
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マウス肝再生過程におけるDNA四重鎖構造の発現動態
石塚 匠, Narantsog Choijookhuu, 甲斐 健吾, 菱川 善隆
⽇本ケミカルバイオロジー学会 第18回年会 (九州工業大学戸畑キャンパス) 2024.5.28
Event date： 2024.5.27 - 2024.5.29
Language：Japanese Presentation type：Poster presentation
Venue：九州工業大学戸畑キャンパス
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肝再生過程におけるDNA四重鎖構造の肝細胞周期への関与
石塚 匠, Narantsog Choijookhuu, 白水 慎一郎, Fidya, 甲斐 健吾, 菱川 善隆
第129回 日本解剖学会総会・全国学術集会 (九州工業大学戸畑キャンパス) 2024.3.22
Event date： 2024.3.21 - 2024.3.23
Language：Japanese Presentation type：Oral presentation (general)
Venue：九州工業大学戸畑キャンパス
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マウス肝再生過程におけるDNA四重鎖構造の肝細胞周期への関与
石塚 匠, Narantsog Choijookhuu, 白水 慎一郎, Fidya, 甲斐 健吾, 菱川 善隆
第65回日本顕微鏡学会九州支部集会 (九州工業大学戸畑キャンパス) 2023.12.9
Event date： 2023.12.9
Language：Japanese Presentation type：Oral presentation (general)
Venue：九州工業大学戸畑キャンパス
Awards 【 display / non-display 】
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2023年度 日本組織細胞化学会 論文賞
2023.10 日本組織細胞化学会
Narantsog Choijookhuu, Yasuaki Shibata, Takumi Ishizuka, Yan Xu, Takehiko Koji, Yoshitaka Hishikawa
Award type：International academic award (Japan or overseas)
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FB3 優秀ポスター賞
2012.7 FB3 organizing committee
石塚匠
Award type：Award from international society, conference, symposium, etc. Country：Sweden
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東京大学大学院工学系研究科長賞（修士）
2008.3 東京大学
石塚匠
Country：Japan
Grant-in-Aid for Scientific Research 【 display / non-display 】
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精子形成過程から解明するグアニン四重鎖構造の生物学的機能
Grant number：24K08641 2024.04 - 2027.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
Authorship：Principal investigator
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細胞内RNA四重鎖を標的とする構造プローブ法の開発
Grant number：21K05314 2021.04 - 2024.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
Authorship：Principal investigator
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分子結合技術を用いた新たな造影剤による革新的がんMRI画像化技術の開発
Grant number：20K08000 2020.04 - 2023.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
Authorship：Coinvestigator(s)
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分子結合技術を用いた造影剤による革新的がんCT画像化技術の開発
Grant number：19K08156 2019.04 - 2022.03
科学研究費補助金 基盤研究(C)
Authorship：Coinvestigator(s)
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高感度蛍光in situハイブリダイゼーション法によるmicroRNA発現解析
Grant number：16K08471 2016.04 - 2019.03
科学研究費補助金 基盤研究(C)
Authorship：Coinvestigator(s)
FRETを利用して、組織切片上で特定の細胞での小分子非翻訳RNAであるmicroRNA発現動態を解析する新たな検出法を開発する。
Other research activities 【 display / non-display 】
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第47回組織細胞化学講習会
2022.08
「In situ hybridization法」の技術講習会Wet Labを行った。
Social Activities 【 display / non-display 】
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解剖見学及び標本示説実習（鵬翔高等学校看護専攻科）
Role(s)： Lecturer
2023.2.1 - 2023.2.2
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解剖見学及び標本示説実習（九州保健福祉大学総合医療専門学校）
Role(s)： Lecturer
2023.1.31
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解剖見学及び標本示説実習（宮崎リハビリテーション学院）
Role(s)： Lecturer
2023.1.23
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解剖見学及び標本示説実習（小林看護医療専門学校）
Role(s)： Lecturer
2023.1.11
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解剖見学及び標本示説実習（小林看護医療専門学校）
Role(s)： Lecturer
2022.9.2