Signaling in Regulation of Podocyte Phenotypes

被引:61
作者
Chuang, Peter Y.
He, John C.
机构
来源
NEPHRON PHYSIOLOGY | 2009年 / 111卷 / 02期
关键词
DIABETIC-NEPHROPATHY; ACTIN CYTOSKELETON; CD2-ASSOCIATED PROTEIN; GLOMERULAR PODOCYTES; NEPHROTIC SYNDROME; KINASE ACTIVATION; GROWTH-FACTOR; APOPTOSIS; NEPHRIN; INJURY;
D O I
10.1159/000191075
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
The kidney podocyte is a terminally differentiated and highly specialized cell. The function of the glomerular filtration barrier depends on the integrity of the podocyte. Podocyte injury and loss have been observed in human and experimental models of glomerular diseases. Three major podocyte phenotypes have been described in glomerular diseases: effacement, apoptosis, and proliferation. Here, we highlight the signaling cascades that are responsible for the manifestation of these pathologic phenotypes. The integrity of the podocyte foot process is determined by the interaction of nephrin with proteins in the slit diaphragm complex, the regulation of actin dynamics by the Rho family of GTPases, and the transduction of extracellular signals through focal adhesion complexes. Activation of the p38 mitogen-activated protein kinase and transforming growth factor-beta 1 causes podocyte apoptosis. Phosphoinositide 3-kinase and its downstream target AKT protect podocytes from apoptosis. In human immunodeficiency virus-associated nephropathy, Src-dependent activation of Stat3, mitogen-activated protein kinase 1,2, and hypoxia-inducible factor 2 alpha is an important driver of podocyte proliferation. At the level of intracellular signaling, it appears that different extracellular signals can converge onto a few pathways to induce changes in the phenotype of podocytes. Copyright (C) 2009 S. Karger AG, Basel
引用
收藏
页码:9 / 15
页数:7
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