| Project/Area Number |
17K07390
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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 |
Cell biology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
堤 弘次 北里大学, 理学部, 助教 (50569853)
斉藤 康二 北里大学, 理学部, 講師 (70556901)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | small GTPase / Rho / Rac / 細胞接着 / 管腔形成 / 細胞間相互作用 / 細胞運動 / E-カドヘリン / smallGTPase / 細胞骨格 / シグナル伝達 / 細胞内情報伝達 |
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| Outline of Final Research Achievements |
The cyst generates extension followed by cell chains and tubules in response to hepatocyte growth factor (HGF). The Rho GTPases play essential roles for tubulogenesis. FilGAP is highly expressed in kidney. Knock-down of FilGAP by siRNA increased the number of extensions in response to HGF, whereas over-expression of FilGAP decreased the number of the extensions. FilGAP is phosphorylated and activated in cells. Over-expression of phospho-mimic FilGAP (ST/D) mutant blocked formation of the membrane extensions induced by HGF in the presence of Y-27632. On the other hand, treatment of the tubules with Y27632 induced scattering of the cells, but FilGAP (ST/D) blocked cell scattering and promoted lumen formation. Moreover, FilGAP seems to stabilize cell-cell interaction through targeting E-cadherin at cell-cell junctions. Taken together, our study suggests that FilGAP may suppress formation of extensions whereas stabilize tubule formation.
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| Academic Significance and Societal Importance of the Research Achievements |
上皮管腔形成は、腎臓、肺、消化管など多くの器官の基本構造であり、その形成機構の解明はきわめて重要である。本研究から、管腔形成におけるFilGAPの役割の一端が明らかになった。FilGAPは動物組織の中で腎臓に高濃度に発現している。MDCK細胞も腎臓由来の細胞であり、本研究成果を腎臓の組織構築や様々な腎疾患のメカニズムの解明に役立てることが期待できる。Rho GTPaseは、上皮管腔形成だけでなく、血管などの内皮管腔構造の形成にも重要な働きをしている。本研究から得られた知見は、上皮、内皮を含めた管腔形成の理解に役立てることができる。
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