Csk regulates angiotensin II-induced podocyte apoptosis
Csk regulates angiotensin II-induced podocyte apoptosis
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Csk 调节血管紧张素 II 诱导的足细胞凋亡
DOI：
10.1007/s10495-016-1256-z
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发表时间：
2016-07-01
期刊：
影响因子：
7.2
通讯作者：
Ding, Guohua
中科院分区：
文献类型：
--
作者：
Zhang, Lu;Ren, Zhilong;Ding, Guohua
越来越多的数据表明，血管紧张素II（Ang II）使足细胞损伤持续存在，并促进终末期肾病的进展。血管紧张素II诱导足细胞凋亡的机制尚未建立。C-末端Src激酶（Csk）是一种与细胞生长、粘附和极化相关的支架蛋白相互作用的胞质激酶，其在细胞凋亡调控中的作用逐渐受到关注。本研究评估Csk在Ang II诱导足细胞凋亡中的作用。在体内，Wistar大鼠随机接受生理盐水或Ang II输注。在体外，我们将分化的小鼠足细胞暴露于Ang II。Ang II增加Csk表达并诱导足细胞凋亡，刺激Csk移位和与Caveolin-1结合，并刺激Fyn pY 416减少，Fyn pY 529增加和nephrin去磷酸化。Csk敲低阻止了Ang II诱导的足细胞凋亡，减少了Fyn激酶的失活，并增加了nephrin和活化形式的Fyn之间的相互作用，同时减少了Csk和Caveolin-1之间的相互作用。这些结果表明，血管紧张素II诱导足细胞损伤通过Csk依赖性途径。
Increasing data have shown that angiotensin II (Ang II) perpetuates podocyte injury and promotes progression to end-stage kidney disease. The mechanism underlying Ang II-induced podocyte apoptosis has not been established. C-terminal Src kinase (Csk) is a cytoplasmic kinase that interacts with scaffolding proteins involved in cell growth, adhesion, and polarization, and the role of Csk in regulating cellular apoptosis has gradually attracted attention. This study evaluates the role of Csk in Ang II-induced podocyte apoptosis. In vivo, Wistar rats were randomly subjected to a normal saline or Ang II infusion. In vitro, we exposed differentiated mouse podocytes to Ang II. Ang II increased Csk expression and induced podocyte apoptosis, stimulated Csk translocation and binding to Caveolin-1, and stimulated decreased Fyn pY416, increased Fyn pY529, and nephrin dephosphorylation. Csk knockdown prevented Ang II-induced podocyte apoptosis, reduced Fyn kinase inactivation, and increased the interaction between nephrin and the activated form of Fyn, accompanied by a reduced interaction between Csk and Caveolin-1. These findings indicate that Ang II induces podocyte injury via a Csk-dependent pathway.