The role of Wnt5a signal in epithelial regeneration in colitis.

• Project/Area Number: 16K08623
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Shiga University of Medical Science
• Principal Investigator: SATO AKIRA 滋賀医科大学, 医学部, 准教授 (70464302)
• 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: Wnt5a / 腸管炎症 / 上皮修復 / 大腸がん / 線維芽細胞

Outline of Final Research Achievements

In this study, we observed that the depletion of Wnt5a suppresses epithelial regeneration process in colitis, suggesting that Wnt5a signal enhances epithelial regeneration in colitis. In addition, we also revealed that Wnt5a signal enhances the inflammation-associated tumor formation in vivo using the AOM/DSS-induced colorectal cancer model. Further we revealed that the expression of Wnt5a in intestinal fibroblasts in colitis is regulated by TGF-beta signaling pathway.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、腸管炎症病態におけるWnt5aの発現制御機構の一端が個体レベルで明らかになり、さらに高発現したWnt5aが炎症病態からの上皮修復過程を増強するばかりでなく、炎症を背景とした大腸がん形成を促進することが明らかになった。そのため、本研究は、Wnt5aシグナルが炎症応答やがんの浸潤・転移ばかりでなく、上皮細胞（がん細胞）の増殖にも関与することが示されたため、学術的に意義が深く、がんを標的とした医療の推進にも貢献するものと考えられる。

Research Products

• [Journal Article] Epithelial membrane protein 1 promotes tumor metastasis by enhancing cell migration via copine-III and Rac1 (2018)
  • Author(s): Ahmat Amin MKB, Shimizu A, Zankov DP, Sato A, Kurita S, Ito M, Maeda T, Yoshida T, Sakaue T, Higashiyama S, Kawauchi A, Ogita H.
  • Journal Title: Oncogene Volume: 37 Pages: 5416-5434
  • DOI: 10.1038/s41388-018-0286-0
  • Peer Reviewed / Open Access
• [Journal Article] Epithelial membrane protein 1 promotes tumor metastasis by enhancing cell migration via copine-III and Rac1. (2018)
  • Author(s): Ahmat Amin, M.K.B., Shimizu, A., Zankov, D.P., Sato, A., Kurita, S., Ito, M., Maeda, T., Yoshida, T., Sakaue, T., Higashiyama, S., Kawauchi, A., and Ogita, H.
  • Journal Title: Oncogene Volume: in press
  • Peer Reviewed
• [Journal Article] Apical secretion of Wnt1 in polarized epithelial cells is regulated by exocyst-mediated trafficking. (2017)
  • Author(s): Yamamoto, H., Sato, A., and Kikuchi, A.
  • Journal Title: J. Biochem. Volume: 162 Pages: 317-326
  • DOI: 10.1093/jb/mvx035
  • NAID: 40021394825
  • Peer Reviewed
• [Journal Article] Differential Effects of Myocardial Afadin on Pressure Overload-Induced Compensated Cardiac Hypertrophy (2017)
  • Author(s): Zankov, D.P., Sato, A., Shimizu, A., and Ogita, H.
  • Journal Title: Circ J Volume: 81 Issue: 12 Pages: 1862-1870
  • DOI: 10.1253/circj.cj-17-0394 10.1253/circj.CJ-17-0394
  • NAID: 130006219260
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] Pathophysiological implications of dipeptidyl peptidases. (2017)
  • Author(s): Sato A, Ogita H.
  • Journal Title: Pathophysiological Implications of Dipeptidyl Peptidases. Volume: - Pages: 843-849
  • DOI: 10.2174/1389203718666170329104936
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Wnt5aシグナルは炎症を背景とした大腸がん形成に促進的に作用する (2016)
  • Author(s): 佐藤 朗、前原 奈都美、扇田 久和、菊池 章
  • Organizer: 第３９回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Remarks] 滋賀医科大学 生化学・分子生物学講座 分子病態生化学部門
  • URL: http://www.shiga-med.ac.jp/~hqbioch2/