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Csk regulates angiotensin II-induced podocyte apoptosis

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Abstract

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.

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Acknowledgments

This study was supported by grants from the National Science Foundation of China (81300559 to Z. Ren and 81270762 to G. Ding).

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    Authors and Affiliations

    1. Division of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Rd., Wuhan, Hubei, 430060, China

      Lu Zhang, Zhilong Ren, Qian Yang & Guohua Ding

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    1. Lu Zhang
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    2. Zhilong Ren
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    3. Qian Yang
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    4. Guohua Ding
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    Correspondence to Guohua Ding.

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    Lu Zhang and Zhilong Ren have contributed equally to this work.

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    Zhang, L., Ren, Z., Yang, Q. et al. Csk regulates angiotensin II-induced podocyte apoptosis. Apoptosis 21, 846–855 (2016). https://doi.org/10.1007/s10495-016-1256-z

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