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

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 and the progression of renal diseases, but its specific mechanism remains unclear. c-Abl is an SH2/SH3 domain–containing nonreceptor tyrosine...

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Autores principales: Yang, Qian, Ma, Yiqiong, Liu, Yipeng, Liang, Wei, Chen, Xinghua, Ren, Zhilong, Wang, Huiming, Singhal, Pravin C., Ding, Guohua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694757/
https://www.ncbi.nlm.nih.gov/pubmed/26510503
http://dx.doi.org/10.1091/mbc.E15-04-0223
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author Yang, Qian
Ma, Yiqiong
Liu, Yipeng
Liang, Wei
Chen, Xinghua
Ren, Zhilong
Wang, Huiming
Singhal, Pravin C.
Ding, Guohua
author_facet Yang, Qian
Ma, Yiqiong
Liu, Yipeng
Liang, Wei
Chen, Xinghua
Ren, Zhilong
Wang, Huiming
Singhal, Pravin C.
Ding, Guohua
author_sort Yang, Qian
collection PubMed
description 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 and the progression of renal diseases, but its specific mechanism remains unclear. c-Abl is an SH2/SH3 domain–containing nonreceptor tyrosine kinase that is involved in cell survival and regulation of the cytoskeleton. Phosphorylated nephrin is able to interact with molecules containing SH2/SH3 domains, suggesting that c-Abl may be a downstream molecule of nephrin signaling. Here we report that Ang II–infused rats developed proteinuria and podocyte damage accompanied by nephrin dephosphorylation and minimal interaction between nephrin and c-Abl. In vitro, Ang II induced podocyte injury and nephrin and Akt dephosphorylation, which occurred in tandem with minimal interaction between nephrin and c-Abl. Moreover, Ang II promoted c-Abl phosphorylation and interaction between c-Abl and SH2 domain–containing 5′-inositol phosphatase 2 (SHIP2). c-Abl small interfering RNA (siRNA) and STI571 (c-Abl inhibitor) provided protection against Ang II–induced podocyte injury, suppressed the Ang II-induced c-Abl–SHIP2 interaction and SHIP2 phosphorylation, and maintained a stable level of nephrin phosphorylation. These results indicate that c-Abl is a molecular chaperone of nephrin signaling and the SHIP2-Akt pathway and that the released c-Abl contributes to Ang II–induced podocyte injury.
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spelling pubmed-46947572016-03-16 Angiotensin II down-regulates nephrin–Akt signaling and induces podocyte injury: roleof c-Abl Yang, Qian Ma, Yiqiong Liu, Yipeng Liang, Wei Chen, Xinghua Ren, Zhilong Wang, Huiming Singhal, Pravin C. Ding, Guohua Mol Biol Cell Articles 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 and the progression of renal diseases, but its specific mechanism remains unclear. c-Abl is an SH2/SH3 domain–containing nonreceptor tyrosine kinase that is involved in cell survival and regulation of the cytoskeleton. Phosphorylated nephrin is able to interact with molecules containing SH2/SH3 domains, suggesting that c-Abl may be a downstream molecule of nephrin signaling. Here we report that Ang II–infused rats developed proteinuria and podocyte damage accompanied by nephrin dephosphorylation and minimal interaction between nephrin and c-Abl. In vitro, Ang II induced podocyte injury and nephrin and Akt dephosphorylation, which occurred in tandem with minimal interaction between nephrin and c-Abl. Moreover, Ang II promoted c-Abl phosphorylation and interaction between c-Abl and SH2 domain–containing 5′-inositol phosphatase 2 (SHIP2). c-Abl small interfering RNA (siRNA) and STI571 (c-Abl inhibitor) provided protection against Ang II–induced podocyte injury, suppressed the Ang II-induced c-Abl–SHIP2 interaction and SHIP2 phosphorylation, and maintained a stable level of nephrin phosphorylation. These results indicate that c-Abl is a molecular chaperone of nephrin signaling and the SHIP2-Akt pathway and that the released c-Abl contributes to Ang II–induced podocyte injury. The American Society for Cell Biology 2016-01-01 /pmc/articles/PMC4694757/ /pubmed/26510503 http://dx.doi.org/10.1091/mbc.E15-04-0223 Text en © 2016 Yang et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Yang, Qian
Ma, Yiqiong
Liu, Yipeng
Liang, Wei
Chen, Xinghua
Ren, Zhilong
Wang, Huiming
Singhal, Pravin C.
Ding, Guohua
Angiotensin II down-regulates nephrin–Akt signaling and induces podocyte injury: roleof c-Abl
title Angiotensin II down-regulates nephrin–Akt signaling and induces podocyte injury: roleof c-Abl
title_full Angiotensin II down-regulates nephrin–Akt signaling and induces podocyte injury: roleof c-Abl
title_fullStr Angiotensin II down-regulates nephrin–Akt signaling and induces podocyte injury: roleof c-Abl
title_full_unstemmed Angiotensin II down-regulates nephrin–Akt signaling and induces podocyte injury: roleof c-Abl
title_short Angiotensin II down-regulates nephrin–Akt signaling and induces podocyte injury: roleof c-Abl
title_sort angiotensin ii down-regulates nephrin–akt signaling and induces podocyte injury: roleof c-abl
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694757/
https://www.ncbi.nlm.nih.gov/pubmed/26510503
http://dx.doi.org/10.1091/mbc.E15-04-0223
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