title: Csk regulates angiotensin II-induced podocyte apoptosis.
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.
authors.affiliation: Division of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Rd., Wuhan, Hubei, 430060, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Rd., Wuhan, Hubei, 430060, China.
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Division of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Rd., Wuhan, Hubei, 430060, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Division of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Rd., Wuhan, Hubei, 430060, China. ghxding@gmail.com.
authors.forename: Guohua
authors.initials: G
authors.lastname: Ding
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D000081247:CSK Tyrosine-Protein Kinase; D051242:Caveolin 1 / Q000378:metabolism; D002478:Cells, Cultured; D008297:Male; D050199:Podocytes / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D051242:Caveolin 1; D000804:Angiotensin II; D000081247:CSK Tyrosine-Protein Kinase; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases
keywords: Angiotensin II; Apoptosis; Csk; Podocyte