Regulatory mechanism of intestinal epithelial cellular life-span

• Project/Area Number: 16K08586
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kobe University
• Principal Investigator: Kotani Taenori 神戸大学, 医学研究科, 助教 (40455960)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 細胞寿命 / 腸上皮細胞 / 腸内容物 / リゾホスファチジン酸 / 常在細菌 / 短鎖脂肪酸 / 神経新生 / 腸内細菌 / ターンオーバー

Outline of Final Research Achievements

The life-span of matured intestinal epithelial cells (IECs) is short (3-4 days), and its regulation is thought to be important for homeostasis of the intestinal epithelium. In this study, we found that short chain fatty acids and lysophosphatidic acids regulated the life-span of IECs in the mouse small intestine. We also found that Mek-Erk signaling and Tsc2-mTORC1 signaling played a key role in regulation of life-span of IECs.

Academic Significance and Societal Importance of the Research Achievements

本研究では、最終分化した細胞の一生を観察する組織として非常に優れている腸管をモデルとして、腸上皮細胞の寿命決定の分子基盤について解明を進めた。本研究の成果は、腸上皮細胞の寿命制御機構の全容解明に寄与出来るだけでなく、腸上皮細胞の寿命制御の破綻に起因する腸炎発症機構の理解についても寄与出来ることが想定され、クローン病や潰瘍性大腸炎を始めとする慢性炎症性腸疾患の治療法や診断法の開発において有力な情報を提供できる可能性がある。

Research Products

• [Journal Article] Role of lysophosphatidic acid in proliferation and differentiation of intestinal epithelial cells (2019)
  • Author(s): Konno T, Kotani T, Setiawan J, Nishigaito Y, Sawada N, Imada S, Saito Y, Murata Y, Matozaki T
  • Journal Title: PLOS ONE Volume: 14 Issue: 4 Pages: e0215255-e0215255
  • DOI: 10.1371/journal.pone.0215255
  • NAID: 120006634675
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of Small Intestinal Epithelial Homeostasis by Tsc2-mTORC1 Signaling (2018)
  • Author(s): Setiawan J, Kotani T, Konno T, Saito Y, Murata Y, Noda T, Matozaki T
  • Journal Title: Kobe J. Med. Sci. Volume: 64
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of Csk in intestinal epithelial barrier function and protection against colitis (2018)
  • Author(s): Sun Chunxiao、Murata Yoji、Imada Shinya、Konno Tasuku、Kotani Takenori、Saito Yasuyuki、Yamada Hideto、Matozaki Takashi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 504 Issue: 1 Pages: 109-114
  • DOI: 10.1016/j.bbrc.2018.08.140
  • NAID: 120006775950
  • Peer Reviewed
• [Journal Article] Regulation by commensal bacteria of neurogenesis in the subventricular zone of adult mouse brain (2018)
  • Author(s): Sawada Naoki、Kotani Takenori、Konno Tasuku、Setiawan Jajar、Nishigaito Yuka、Saito Yasuyuki、Murata Yoji、Nibu Ken-ichi、Matozaki Takashi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 498 Issue: 4 Pages: 824-829
  • DOI: 10.1016/j.bbrc.2018.03.064
  • NAID: 120006733123
  • Peer Reviewed
• [Journal Article] Anti-human SIRPα antibody is a new tool for cancer immunotherapy (2018)
  • Author(s): Murata Yoji、Tanaka Daisuke、Hazama Daisuke、Yanagita Tadahiko、Saito Yasuyuki、Kotani Takenori、Oldenborg Per-Arne、Matozaki Takashi
  • Journal Title: Cancer Science Volume: 印刷中 Issue: 5 Pages: 1300-1308
  • DOI: 10.1111/cas.13548
  • NAID: 120006482611
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] SIRPα+dendritic cells regulate homeostasis of fibroblastic reticular cells via TNF receptor ligands in the adult spleen (2017)
  • Author(s): Saito Yasuyuki、Respatika Datu、Komori Satomi、Washio Ken、Nishimura Taichi、Kotani Takenori、Murata Yoji、Okazawa Hideki、Ohnishi Hiroshi、Kaneko Yoriaki、Yui Katsuyuki、Yasutomo Koji、Nishigori Chikako、Nojima Yoshihisa、Matozaki Takashi
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 114 Issue: 47
  • DOI: 10.1073/pnas.1711345114
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Promotion of intestinal epithelial cell turnover by commensal bacteria: role of short-chain fatty acids. (2016)
  • Author(s): Park J.H., Kotani T., Konno T., Setiawan J., Kitamura Y., Imada S., Usui Y., Hatano N., Shinohara M., Saito Y., Murata Y., and Matozaki T.
  • Journal Title: PloS One Volume: 11 Issue: 5 Pages: e0156334-e0156334
  • DOI: 10.1371/journal.pone.0156334
  • NAID: 120005774020
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Role of Tsc2-mTORC1 signaling in homeostasis of intestinal epithelium and its relation to inflammation and cancer (2019)
  • Author(s): Takenori Kotani,Jajar Setiawan,Yoji Murata,Yasuyuki Saito,Takashi Matozaki
  • Organizer: American Association for Cancer Research (AACR) Annual Meeting 2019
  • Int'l Joint Research
• [Presentation] Role of the tyrosine phosphorylation signal in homeostasis of intestinal epithelium and its relation to inflammation and cancer (2018)
  • Author(s): Takashi Matozaki,Yoji Murata,Takenori Kotani,Yasuyuki Saito
  • Organizer: ICPP13(プロテインホスファターゼ)
  • Int'l Joint Research
• [Presentation] Tsc2-mTORC1シグナルによる小腸上皮の恒常性制御 (2018)
  • Author(s): ジャジャル セティアワン、小谷 武徳、金野 祐、村田 陽二、齊藤 泰之、的崎 尚
  • Organizer: 第77回日本癌学会総会
• [Presentation] 腸炎症制御における腸上皮Srcファミリーキナーゼの役割 (2018)
  • Author(s): 孫 春暁、村田 陽二、今田 慎也、小谷 武徳、齊藤 泰之、山田 秀人、的崎 尚
  • Organizer: 第77回日本癌学会総会
• [Presentation] 常在細菌による成体マウス脳室下帯におけるニュートロン新生の制御 (2018)
  • Author(s): 澤田 直樹、小谷 武徳、金野 祐、ジャジャル セティアワン、齊藤 泰之、村田 陽二、丹生 健一、的崎 尚
  • Organizer: 第91回日本生化学会大会
• [Presentation] Srcファミリーキナーゼの炎症性腸疾患における重要性 (2018)
  • Author(s): 孫 春暁、村田 陽二、今田 慎也、小谷 武徳、齊藤 泰之、山田 秀人、的崎 尚
  • Organizer: 第91回日本生化学会大会
• [Presentation] 腸上皮細胞の恒常生維持に関わるチロシンリン酸化シグナルの意義 (2018)
  • Author(s): 的崎 尚、村田 陽二、小谷 武徳、齊藤 泰之
  • Organizer: 第91回日本生化学会大会
• [Presentation] 成体マウス脳室下帯における神経新生の常在細菌による制御 (2018)
  • Author(s): 澤田 直樹、小谷 武徳、金野 祐、Jajar Setiawan、齊藤 泰之、村田 陽二、的崎 尚
  • Organizer: 第65回日本生化学会近畿支部例会
• [Presentation] Role of Csk in the regulation of intestinal homeostasis and the development of inflammation in the colon (2018)
  • Author(s): Chunxiao Sun,Yoji Murata,Shinya Imada,Takenori Kotani,Yasuyuki Saito,Hideto Yamada,and Takashi Matozaki
  • Organizer: 第65回日本生化学会近畿支部例会
• [Presentation] Regulation of intestinal immunity by the microvillus-specific protein tyrosine phosphatase SAP-1 and its substrate CEACAM20 (2017)
  • Author(s): Takenori Kotani, Yoji Murata, Yana Supriatna, Yasuaki Kitamura, Shinya Imada, Yasuyuki Saito, Hideki Okazawa, Hiroshi Ohnishi, Takashi Matozaki
  • Organizer: Europhosphatase 2019: Phosphatases in cell fates and decisions
  • Int'l Joint Research
• [Presentation] Role of Tsc2-mTORC1 signaling in intestinal homeostasis 腸上皮の恒常性におけるTsc2-mTORC1シグナルの役割 (2017)
  • Author(s): Takenori Kotani, Jajar Setiawan, Tasuku Konno, Shinya Imada, Naoki Sawada, Yoji Murata, Yasuyuki Saito, Takashi Matozaki
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] Role of mechanistic target of rapamycin complex 1 (mTORC1) in regulation of intestinal epithelial homeostasis (2017)
  • Author(s): Takenori Kotani, Jajar Setiawan, Tasuku Konno, Shinya Imada, Naoki Sawada, Yoji Murata, Yasuyuki Saito, Takashi Matozaki
  • Organizer: 第8回日本プロテインホスファターゼ研究会 学術集会
• [Presentation] Role of Tsc2-mTORC1 signaling in regulation of intestinal epithelial homeostasis (2017)
  • Author(s): Jajar Setiawan, Takenori Kotani, Tasuku Konno, Shinya Imada, Jung-ha Park, Naoki Sawada, Yasuyuki Saito, Yoji Murata, Takashi Matozaki
  • Organizer: 2017年度生命科学系学会合同年次大会(第40回日本分子生物学会・第90回日本生化学会)
• [Presentation] 腸内容物による腸上皮細胞のターンオーバー制御 (2017)
  • Author(s): 金野 祐、小谷 武徳、朴 貞河、Jajar Setiawan、澤田 直樹、西垣内 佑香、波多野 直哉、岡田 雅人、篠原 正和、齊藤 泰之、村田 陽二、的崎 尚
  • Organizer: 第16回生体機能研究会
• [Presentation] Short chain fatty acids regulate the turnover of intestinal epithelial cells (2016)
  • Author(s): Konno T., Kotani T., Park J.H., Setiawan J., Kitamura Y., Imada S., Usui Y., Hatano N., Shinohara M., Saito Y., Murata Y., and Matozaki T.
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台市
  • Year and Date: 2016-09-25
• [Remarks] 神戸大学大学院医学研究科 生化学・分子生物学講座 シグナル統合学分野大学院医学研究科
  • URL: http://www.med.kobe-u.ac.jp/tougou/signal/Home.html
• [Remarks] 神戸大学大学院医学研究科生化学・分子生物学講座シグナル統合学分野
  • URL: http://www.med.kobe-u.ac.jp/tougou/signal/Home.html