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IQGAP1 mediates angiotensin II-induced apoptosis of podocytes via the ERK1/2 MAPK signaling pathway.

Authors: Liu, Y  Liang, W  Yang, Q  Ren, Z  Chen, X  Zha, D  Singhal, PC  Ding, G 
Citation: Liu Y, etal., Am J Nephrol. 2013;38(5):430-44. doi: 10.1159/000355970. Epub 2013 Nov 12.
Pubmed: (View Article at PubMed) PMID:24247724
DOI: Full-text: DOI:10.1159/000355970

BACKGROUND/AIMS: The mechanism underlying angiotensin II (AngII)-promoted podocyte apoptosis has not been established. IQ domain GTPase-activating protein 1 (IQGAP1) is a scaffolding protein of the mitogen-activated protein kinases (MAPK) signaling pathway, and plays a significant role in apoptosis. The present study evaluates the role of IQGAP1 in AngII-induced podocyte apoptosis. METHODS: We randomly assigned 36 male Wistar rats to a normal saline-infused group, an AngII-infused group, or a normal control group, and measured podocyte apoptosis by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and transmission electron microscopic analysis. In addition, we exposed differentiated mouse podocytes to AngII and then assessed apoptosis by flow cytometry and Hoechst-33258 staining. Expression of IQGAP1 was measured by Western blotting, real-time PCR and immunofluorescence assay in vivo and in vitro. IQGAP1 siRNA and MAPK pathway inhibitors were further introduced to investigate the role of IQGAP1 and MAPK signaling in the process. Coimmunoprecipitation was used to evaluate the interaction between ERK1/2 and IQGAP1. RESULTS: AngII promoted podocyte apoptosis in vivo and in vitro. IQGAP1 had a linear distribution along the capillary loops of glomeruli in vivo, and was in the cellular membrane and cytoplasm of cultured podocytes. AngII stimulated IQGAP1 expression and increased phosphorylation of P38, JNK, and ERK1/2. Knockdown of IQGAP1 with siRNA prevented AngII-induced apoptosis of podocytes and reduced AngII-induced phosphorylation of ERK1/2, but not that of P38, JNK. This was accompanied by a reduced interaction between ERK1/2 and IQGAP1. CONCLUSION: IQGAP1 contributes to AngII-induced apoptosis of podocytes by interacting with the ERK1/2 signaling protein.


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RGD Object Information
RGD ID: 11049550
Created: 2016-04-08
Species: All species
Last Modified: 2016-04-08
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.