HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/F202    most recent 00468.2007v1 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 Citing Articles Citing Articles via HighWire Google Scholar Articles by Mao, H. Articles by Yu, X. PubMed PubMed Citation Articles by Mao, H. Articles by Yu, X.

HSP72 attenuates renal tubular cell apoptosis and interstitial fibrosis in obstructive nephropathy

¹Department of Nephrology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; ²Renal Section, Department of Medicine, Boston Medical Center, Boston University, Boston, Massachusetts; ³Laboratory for Kidney Pathology, Incorporated, Nashville, Tennessee; and ⁴Department of Medicine, Brown University School of Medicine, Providence, Rhode Island

Submitted 9 October 2007 ; accepted in final form 14 April 2008

Although heat shock protein 72 kDa (HSP72) protects tubular epithelium from a variety of acute insults, its role in chronic renal injury and fibrosis is poorly characterized. In this study, we tested the hypothesis that HSP72 reduces apoptosis and epithelial-to-mesenchymal transition (EMT), important contributors to tubular cell injury in vitro and in vivo. In rats, orally administered geranylgeranylacetone (GGA), an agent that selectively induces HSP72, markedly reduced both apoptosis and cell proliferation in tubular epithelium and decreased both interstitial fibroblast accumulation and collagen I deposition after unilateral ureteric obstruction, a model of chronic renal tubulointerstitial fibrosis and dysfunction. In cultured renal NRK52E cells, exposure to TGF-β1 induced EMT and apoptosis, major causes of renal fibrosis and tubular atrophy, respectively. Exposure to a pan-caspase inhibitor (ZVAD-FMK) prevented TGF-β1-induced apoptosis but did not reduce EMT. In contrast, selective HSP72 expression in vitro inhibited EMT caused by TGF-β1 as indicated by preserving the E-cadherin expression level and -smooth muscle actin induction. Small interfering RNA directed against HSP72 blocked the cytoprotective effects of HSP72 overexpression on EMT in TGF-β1-exposed cells. Taken together, our data indicate that HSP72 ameliorates renal tubulointerstitial fibrosis in obstructive nephropathy by inhibiting both renal tubular epithelial cell apoptosis and EMT.

heat stress protein 72 kDa; epithelial-to-mesenchymal transition, -smooth muscle actin, E-cadherin, transforming growth factor-β1

This article has been cited by other articles:

				A. Vidyasagar, S. Reese, Z. Acun, D. Hullett, and A. Djamali HSP27 is involved in the pathogenesis of kidney tubulointerstitial fibrosis Am J Physiol Renal Physiol, September 1, 2008; 295(3): F707 - F716. [Abstract] [Full Text] [PDF]