Angiotensin II down-regulates nephrin–Akt signaling and induces podocyte injury: role of c-Abl

• DOI: 10.1091/mbc.e15-04-0223
• Publication Date: 2015-10-29T03:05:20Z
• Authors: Qian Yang; Yiqiong Ma; Yipeng Liu; Wei Liang; Xinghua Chen; Zhilong Ren; Huiming Wang; Pravin C. Singhal; Guohua Ding
• Keywords: Nephrin; ABL; Dephosphorylation; Slit diaphragm

Recent studies have shown that nephrin plays a vital role in angiotensin II (Ang II)-induced podocyte injury and thus contributes to the onset of proteinuria progression renal diseases, but its specific mechanism remains unclear. c-Abl is an SH2/SH3 domain-containing nonreceptor tyrosine kinase involved cell survival regulation cytoskeleton. Phosphorylated able interact with molecules containing domains, suggesting may be downstream molecule signaling. Here we report Ang II-infused rats developed damage accompanied by dephosphorylation minimal interaction between c-Abl. In vitro, induced Akt dephosphorylation, which occurred tandem Moreover, promoted phosphorylation SH2 5'-inositol phosphatase 2 (SHIP2). small interfering RNA (siRNA) STI571 (c-Abl inhibitor) provided protection against II-induced injury, suppressed c-Abl-SHIP2 SHIP2 phosphorylation, maintained stable level phosphorylation. These results indicate molecular chaperone signaling SHIP2-Akt pathway released injury.