2022 Fiscal Year Final Research Report
Elucidation of a novel actin remodeling mechanism that supports the filtration apparatus of blood formed by podocytes
| Project/Area Number |
20K08591
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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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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
竹居 孝二 岡山大学, 医歯薬学域, 教授 (40322226)
淺沼 克彦 千葉大学, 大学院医学研究院, 教授 (60449064)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | タンパク尿 / ポドサイト / ダイナミン / アクチン / 微小管 / 透過型電子顕微鏡 / in vitro / 細胞骨格 |
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| Outline of Final Research Achievements |
Glomerular podocytes in kidney play important roles in filtering blood and preventing the development of proteinuria. Podocytes adhere to capillaries via a basement membrane to form an elaborated filtration apparatus of blood. Therefore, maintaining the morphology and function of podocytes is important to prevent progression of proteinuria, but the mechanism is largely unknown. We focused on the functions of dynamin 1 and dynamin 2 proteins expressed in podocytes. Both proteins have been shown to be essential for maintaining the morphology and function of podocytes, but their molecular mechanisms remained to be elucidated. In this study, we found that both dynamins are involved in the regulation of the cytoskeleton that supports podocyte morphology. Dynamin 1 and dynamin 2 bundled and stabilized microtubules and actin filaments, respectively.
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| Free Research Field |
生化学
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| Academic Significance and Societal Importance of the Research Achievements |
腎臓糸球体ポドサイトは、血液を濾過し蛋白尿の発生を防ぐ中心的な役割を持っている。このため、ポドサイトの障害により血液濾過装置が破綻すると、透析治療が必要な慢性腎不全の進行に直結する。本研究では、ポドサイトの形態・機能の維持に重要なダイナミンによる微小管、アクチン線維束化機構の一端を明らかにできた。さらに、ダイナミンの活性化はポドサイトのアクチン細胞骨格の再構成のみならず接着能も促進することから、ポドサイトの保護や機能改善に働くダイナミンをターゲットとした創薬が大いに期待される。
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