The cytoprotective role of Ras in complement-mediated glomerular epithelial cell injury

被引：4
作者：
Huynh, Carl
Ren, Guohui
Papillon, Joan
Guillemette, Julie
Takano, Tomoko
Cybulsky, Andrey V.
机构：
[1] McGill Univ, Dept Physiol, Montreal, PQ, Canada
[2] McGill Univ, Dept Med, Montreal, PQ, Canada
来源：
CLINICAL IMMUNOLOGY | 2009年 / 131卷 / 02期
关键词：
Actin; Cytoskeleton; Rho GTPases; Protein kinases; ACTIVATED PROTEIN-KINASE; PHOSPHOINOSITIDE 3-OH KINASE; ACTIN CYTOSKELETON; CYTOCHALASIN-D; EXTRACELLULAR-MATRIX; RHO ACTIVITY; PATHWAY; APOPTOSIS; MEMBRANE; SURVIVAL;
D O I：
10.1016/j.clim.2008.11.012
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
In experimental membranous nephropathy, complement C5b-9-induced glomerular epithelial, cell (GEC) injury leads to toss of glomerular permselectivity and proteinuria. Incubation of cultured GEC with antibody and serially-increasing concentrations of complement induced cytotoxicity in a dose-dependent manner. Stable expression of constitutively-active Ras (V(12)Ras) in GEC attenuated injury significantly. In the V(12)Ras-expressing GEC, disruption of the F-actin cytoskeleton with latrunculin B or swinholide A, or stabilization of F-actin with jaspiakinolide reversed the cytoprotective effect of V(12)Ras. GEC displayed cortical F-actin; V(12)Ras-expressing GEC showed smaller and more rounded morphology, and decreased activity of the Rho GTPase, Rac1, compared with control GEC. Thus, the protective effect of V(12)Ras is dependent on remodeling of the actin cytoskeleton, and may be associated with a reduction in Rac activity, thereby altering the equilibrium in the activities of Rho GTPases. Activation of Ras signaling is a novel pathway to consider in developing strategies for cytoprotection in comptement-mediated injury. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码：343 / 353
页数：11
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