title: IQGAP1 mediates angiotensin II-induced apoptosis of podocytes via the ERK1/2 MAPK signaling pathway.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  IQGAP1 contributes to AngII-induced apoptosis of podocytes by interacting with the ERK1/2 signaling protein.
authors.affiliation: Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Ren
authors.forename: Xinghua
authors.initials: X
authors.lastname: Chen
authors.forename: Dongqing
authors.initials: D
authors.lastname: Zha
authors.forename: Pravin C
authors.initials: PC
authors.lastname: Singhal
authors.forename: Guohua
authors.initials: G
authors.lastname: Ding
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D018450:Disease Progression; D005786:Gene Expression Regulation; D007678:Kidney Glomerulus / Q000187:drug effects; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D050199:Podocytes / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D020703:ras GTPase-Activating Proteins / Q000502:physiology*
chemical_list: C101203:IQ motif containing GTPase activating protein 1; D020703:ras GTPase-Activating Proteins; D000804:Angiotensin II; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3