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This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/F707    most recent 90240.2008v1 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 Vidyasagar, A. Articles by Djamali, A. PubMed PubMed Citation Articles by Vidyasagar, A. Articles by Djamali, A.

HSP27 is involved in the pathogenesis of kidney tubulointerstitial fibrosis

Nephrology Section, Department of Medicine, University of Wisconsin Madison School of Medicine and Public Health, Madison, Wisconsin

Submitted 7 April 2008 ; accepted in final form 30 June 2008

We hypothesized that heat shock protein 27 (HSP27), a small heat shock protein with actin-remodeling properties, is involved in the pathogenesis of kidney tubulointerstitial fibrosis. We first examined its expression in the rat unilateral ureteral obstruction (UUO) model of kidney fibrosis and epithelial-to-mesenchymal transition (EMT). Immunoblot analyses showed that UUO resulted in significant upregulation of TGF-β1, -smooth muscle actin (-SMA), total and phosphorylated HSP27, and phosphorylated p38MAPK. Immunofluorescence studies showed that HSP27 costained with TGF-β1, -SMA, and E-cadherin in areas of tubulointerstitial injury. We next attempted to translate these studies in an in vitro model of EMT using rat proximal tubular epithelial cells (NRK52E). TGF-β1 (20 ng/ml) treatment resulted in EMT (upregulation of -SMA and downregulation of E-cadherin) and significant upregulation of total and phosphorylated HSP27 and p38MAPK after 3 days. Real-time PCR analyses showed that HSP27, vimentin, and fibronectin increased whereas E-cadherin mRNA levels decreased. Double-staining immunofluorescence studies showed intracytoplasmic colocalization of HSP27 with both F-actin and E-cadherin in cells undergoing EMT. HSP27 overexpression by transient transfection significantly increased E-cadherin while decreasing E-cadherin repressor Snail levels. In aggregate, these studies show that HSP27 is involved in the pathogenesis of TGF-β1-induced EMT and chronic tubulointerstitial fibrosis. HSP27 overexpression may delay injury by upregulating E-cadherin through downregulation of Snail.

epithelial-to-mesenchymal transition; E-cadherin; NRK52E cells; ureteral obstruction