TGF-β1 regulates the PINCH-1-integrin-linked kinase-α-parvin complex in glomerular cells

被引:34
作者
Jung, Kyu Yong
Chen, Ka
Kretzler, Matthias
Wu, Chuanyue
机构
[1] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA
[2] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2007年 / 18卷 / 01期
关键词
D O I
10.1681/ASN.2006050421
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
Glomerular damage is a major cause of renal failure. Recent studies suggest that a ternary protein complex that consists of PINCH-1, integrin-linked kinase, and a-parvin, cytoplasmic components of cell-extracellular matrix adhesions, plays pivotal roles in regulation of glomerular cell behavior. It is reported here that TGF-beta 1, a key factor in the progression of glomerular failure, regulates the PINCH-1-integrin-linked kinase-a-parvin (PIP) complex formation in glomerular podocytes and mesangial cells. Treatment of podocytes with TGF-beta 1 inhibited the PIP complex formation. Forced disruption of the PIP complex in podocytes activated p38 mitogen-activated protein kinase and promoted apoptosis. Importantly, inhibition of p38 mitogen-activated protein kinase, either with a chemical p38 inhibitor (SB202190) or with a dominant negative form of p38 alpha, alleviates podocyte apoptosis that is induced by the disruption of the PIP complex. In contrast to an inhibitory role in podocytes, TGF-beta 1 promotes the PIP complex formation in mesangial cells. Thus, TGF-beta 1 regulates the PIP complex in a cell type-dependent manner. Because the PIP complex promotes glomerular mesangial matrix deposition and protects podocytes from apoptosis, the TGF-beta 1-induced up- and downregulation of the PIP complex likely contribute to the pleiotropic effects of TGF-beta 1 on different glomerular cell types and hence the progression of glomerular failure.
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页码:66 / 73
页数:8
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