HSP75 inhibits TGF-β1-induced apoptosis by targeting mitochondria in human renal proximal tubular epithelial cells

Abstract

Heat shock protein 75 (HSP75, also known as TRAP1) as a member of the Hsp90 molecular chaperone family, has been implicated in the progression of renal fibrosis. Apoptosis of renal tubular cells is known to be the critical mechanisms of the progression of renal fibrosis, and mitochondrial dysfunction participates in this process. In this study, we investigated the effects of HSP75 on mitochondrial dysfunction and its relevance to apoptosis in human renal proximal tubular cells (HK2). HSP75 was up- and down-regulated in HK2 cells treated with TGF-β1 using letiviral vectors. HSP75 improved mitochondrial morphological injury and stabilized mitochondrial functions in HK2 cells stimulated by TGF-β1. Overexpression of HSP75 inhibited cell apoptosis, and it was reversed by using HSP75 shRNAs. HSP75 may be important for maintenance of mitochondrial function in HK2 cells under pathological conditions. Activation of HSP75 may be therapeutically useful in renal fibrosis to promote and maintain normal mitochondrial functions.

Keywords: Apoptosis; Heat shock protein 75; Mitochondria; Renal fibrosis.