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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/F253    most recent 00070.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Shi, X. Articles by Wu, C. PubMed PubMed Citation Articles by Shi, X. Articles by Wu, C.

Roles of PINCH-2 in regulation of glomerular cell shape change and fibronectin matrix deposition

¹Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania; and ²Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan

Submitted 7 February 2008 ; accepted in final form 12 May 2008

The PINCH-1-integrin-linked kinase (ILK)--parvin (PIP) complex plays important roles in the regulation of glomerular cell behavior, including podocyte shape change, apoptosis, and mesangial fibronectin matrix deposition. In this study, we show that PINCH-2, a protein that is structurally related to PINCH-1 but encoded by a different gene, is coexpressed with PINCH-1 in podocytes. Treatment of podocytes with transforming growth factor (TGF)-β1 elevated the level of PINCH-2, resulting in increased association of PINCH-2 with ILK and -parvin and concomitant displacement of PINCH-1 from the PIP complex. To gain insights into the functional consequences of elevated PINCH-2 expression, we overexpressed PINCH-2 in podocytes by infection with an adenovirus encoding PINCH-2. Overexpression of PINCH-2 resulted in displacement of PINCH-1 from the PIP complex and compromised podocyte spreading. The PINCH-2-mediated displacement of PINCH-1, however, did not prompt apoptosis. Interestingly, the effect of PINCH-2 on podocyte spreading depends on differentiation status, as overexpression of PINCH-2 in podocytes that were not fully differentiated did not alter cell spreading. Finally, we show that overexpression of PINCH-2 in mesangial cells resulted in displacement of PINCH-1 from the PIP complex but impaired neither mesangial cell spreading nor fibronectin matrix deposition. These studies suggest that PINCH-2 can substitute for PINCH-1 in at least certain processes in glomerular cells (e.g., podocyte survival signaling and mesangial fibronectin matrix deposition), albeit that an aberrantly high level of PINCH-2 may contribute to TGF-β1-induced alteration in podocyte shape modulation.

TGF-β1; ILK; parvin; podocytes; mesangial cells; cell spreading; fibronectin matrix assembly