Involvement of the Wnt5a-Ror2 signaling in colitis
| Project/Area Number |
24590378
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
SATO AKIRA 大阪大学, 医学(系)研究科(研究院), 助教 (70464302)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | Wnt5a-Ror2シグナル / 腸管炎症 / 樹状細胞 / Th1細胞 / IFN-γ-STAT1シグナル / β-カテニン非依存性経路 / IL-12 / Wnt5a / Ror2 / IFNγ-STAT1シグナル / 炎症性サイトカイン / IFN-γ / 遺伝子改変マウス / Wntシグナル伝達経路 |
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| Outline of Final Research Achievements |
It has been suggested that post-natal abnormalities in Wnt5a signaling are involved in inflammatory diseases, however the mechanism is not well understood. I examined the role of Wnt5a signaling in intestinal immunity using conditional knockout mice for Wnt5a and its receptor Ror2. Removing Wnt5a or Ror2 suppressed dextran sodium sulfate (DSS)-induced colitis. It also attenuated the DSS-dependent increase in inflammatory cytokine expression and suppressed IFN-γ-producing CD4+ Th1 cells in the colon. Wnt5a was expressed by stromal fibroblasts in ulcerative lesions in DSS-treated mice and inflammatory bowel disease patients. In vitro experiments demonstrated that the Wnt5a-Ror2 signaling axis augmented the dendritic cell (DC) priming effect of IFN-γ, leading to enhanced IL-12 expression. Taken together, these results suggest that the Wnt5a produced by stromal fibroblasts promotes IFN-γ signaling, leading to IL-12 expression in DCs, and thereby inducing Th1 polarization in colitis.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Wnt5a promotes cancer cell invasion and proliferation by receptor-mediated endocytosis-dependent and -independent mechanisms, respectively2015
Author(s)
Shojima, K., Sato, A., Hanaki, H., Tsujimoto, I., Nakamura, M., Hattori, K., Sato, Y., Dohi, K., Hirata, M., Yamamoto, H., and Kikuchi, A.
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Journal Title
Sci. Rep.
Volume: 5
Issue: 1
Pages: 8042-8042
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] A combination of Wnt and growth factor signaling induces Arl4c expression to form epithelial tubular structures.2014
Author(s)
Matsumoto, S., Fujii, S., Sato, A., Ibuka, S., Kagawa, Y., Ishii, M., and Kikuchi, A.
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Journal Title
EMBO J
Volume: 33
Issue: 7
Pages: 702-718
DOI
Related Report
Peer Reviewed
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