Fyn Mediates High Glucose-Induced Actin Cytoskeleton Reorganization of Podocytes via Promoting ROCK Activation In Vitro.
Fyn Mediates High Glucose-Induced Actin Cytoskeleton Reorganization of Podocytes via Promoting ROCK Activation In Vitro.
复制标题
Fyn 通过促进体外 ROCK 激活介导高葡萄糖诱导的足细胞肌动蛋白细胞骨架重组
DOI：
10.1155/2016/5671803
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发表时间：
2016
影响因子：
4.3
通讯作者：
Wang R
中科院分区：
文献类型：
--
作者：
Lv Z;Hu M;Ren X;Fan M;Zhen J;Chen L;Lin J;Ding N;Wang Q;Wang R
Fyn是酪氨酸激酶Src家族的一员，是多种细胞类型中细胞骨架重塑的关键调节因子。最近的研究表明，Fyn负责nephrin酪氨酸磷酸化，这将导致肌动蛋白丝聚合和足细胞损伤。因此，Fyn在足细胞中的详细参与有待阐明。在这项研究中，我们研究了Fyn/ROCK信号通路的潜在作用及其与paxillin的相互作用。我们的研究结果表明，高葡萄糖导致足细胞中丝状肌动蛋白（F-actin）重排，伴随着paxillin磷酸化和细胞运动性增加，在此期间Fyn和ROCK被明显激活。siRNA敲低Fyn基因对高糖诱导的足细胞损伤和ROCK激活具有逆转作用；抑制ROCK对Fyn磷酸化无显著影响。这些观察结果表明，体外Fyn通过促进ROCK激活和paxillin磷酸化介导高糖诱导的足细胞肌动蛋白细胞骨架重塑。
Fyn, a member of the Src family of tyrosine kinases, is a key regulator in cytoskeletal remodeling in a variety of cell types. Recent studies have demonstrated that Fyn is responsible for nephrin tyrosine phosphorylation, which will result in polymerization of actin filaments and podocyte damage. Thus detailed involvement of Fyn in podocytes is to be elucidated. In this study, we investigated the potential role of Fyn/ROCK signaling and its interactions with paxillin. Our results presented that high glucose led to filamentous actin (F-actin) rearrangement in podocytes, accompanied by paxillin phosphorylation and increased cell motility, during which Fyn and ROCK were markedly activated. Gene knockdown of Fyn by siRNA showed a reversal effect on high glucose-induced podocyte damage and ROCK activation; however, inhibition of ROCK had no significant effects on Fyn phosphorylation. These observations demonstrate that in vitro Fyn mediates high glucose-induced actin cytoskeleton remodeling of podocytes via promoting ROCK activation and paxillin phosphorylation.