Regulation of intestinal immunity by an intestinal epithelial-specific protein tyrosine phosphatase

• Project/Area Number: 16K08624
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kobe University
• Principal Investigator: Murata Yoji 神戸大学, 医学研究科, 准教授 (60400735)
• 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: チロシンホスファターゼ / 腸上皮細胞 / 腸管免疫 / 腸炎 / がん / 炎症性腸疾患 / 大腸がん / 腸内細菌

Outline of Final Research Achievements

In this study, I showed, by using gene-modified mice, that CEACAM20, Src family kinases, and Csk, which are signaling molecules related to the intestinal epithelial-specific protein tyrosine phosphatase SAP-1, were involved in the pathogenesis of colitis, and I revealed some of the molecular mechanisms for the regulation of immune responses in the intestine by these molecules in intestinal epithelial cells.

Academic Significance and Societal Importance of the Research Achievements

腸管における免疫応答の異常は大腸炎や大腸がんの病態形成に深く関わることが知られている。しかしながら、腸管を構成する腸上皮細胞による免疫制御機構については不明な点が多い。本研究により、腸上皮細胞による腸管免疫制御機構の一端が明らかとなった。また、その制御機構の異常が腸炎の病態形成に関わることが腸炎モデル動物を用いた解析から示唆された。今後、更に本研究を進めることにより、免疫異常と関連する腸炎や大腸がんなどの消化管疾患の新たな診断法や治療法の開発の糸口が得られることが期待される。

Research Products

• [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] Microvillus-specific protein tyrosine phosphatase SAP-1 plays a role in regulating the intestinal paracellular transport of macromolecules. (2017)
  • Author(s): Mori S, Kamei N, Murata Y, Takayama K, Matozaki T, Takeda-Morishita M.
  • Journal Title: J Pharm Sci. Volume: 106 Issue: 9 Pages: 2904-2908
  • DOI: 10.1016/j.xphs.2017.04.014
  • Peer Reviewed
• [Journal Article] Role of Src family kinases in regulation of intestinal epithelial homeostasis. (2016)
  • Author(s): Imada S, Murata Y, Kotani T, Hatano M, Sun C, Konno T, Park JH, Kitamura Y, Saito Y, Ohdan H, Matozaki T.
  • Journal Title: Mol Cell Biol Volume: 36 Issue: 22 Pages: 2811-2823
  • DOI: 10.1128/mcb.00311-16
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Future therapeutic potential of SAP-1 in inflammatory bowel diseases (2016)
  • Author(s): Kotani T, Murata Y, Saito Y, Matozaki T.
  • Journal Title: Expert Rev Gastroenterol Hepatol. Volume: 10 Issue: 12 Pages: 1313-1315
  • DOI: 10.1080/17474124.2016.1245144
  • Peer Reviewed
• [Presentation] Role of Csk in the regulation of intestinal homeostasis and the development of inflammation in the colon (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65回日本生化学会近畿支部例会
• [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] 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] Role of Src family kinases in regulation of intestinal epithelial homeostasis. (2017)
  • Author(s): Murata Y, Imada S, Kotani T, Sun C, Saito Y, and Matozaki T.
  • Organizer: Europhosphatase 2018: Phosphatases in cell fates and decisions
  • Int'l Joint Research
• [Presentation] Regulation of intestinal immunity by the microvillus-specific protein tyrosine phosphatase SAP-1 and its substrate CEACAM20. (2017)
  • Author(s): Kotani T, Murata Y, Supriatna Y, Kitamura Y, Imada S, Saito Y, Okazawa H, Ohnishi H, and Matozaki T.
  • Organizer: Europhosphatase 2018: Phosphatases in cell fates and decisions
  • Int'l Joint Research
• [Presentation] Regulation of interestinal epithelial homeostasis by Src family kinases through Rac and YAP. (2017)
  • Author(s): Murata Y, Imada S, Kotani T, Sun C, Saito Y, and Matozaki T.
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] Role of Src family kinases in regulatin of intestinal epithelial homeostasis (2016)
  • Author(s): Shinya Imada, Yoji Murata, Takenori Kotani, Masaki Hatano, Chunxiao Sun, Tasuku Konno, Yasuyuki Saito, Hideki Ohdan, Takahi Matozaki
  • Organizer: 第12回プロテインホスファターゼ国際カンファレンス ＆ 革新がんゲノム国際シンポジウム
  • Place of Presentation: 近畿大学東 大阪キャンパス
  • Year and Date: 2016-10-27
  • Int'l Joint Research
• [Presentation] 受容体型チロシンホスファターゼSAP-1による腸管免疫制御 (2016)
  • Author(s): 村田 陽二、小谷 武徳、齊藤 泰之、的崎 尚
  • Organizer: 第15回生体機能研究会
  • Place of Presentation: 淡路夢舞台国際会議場
  • Year and Date: 2016-07-01
• [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