Ketamine-induced bladder fibrosis involves epithelial-to-mesenchymal transition mediated by transforming growth factor- β1.

Ketamine-induced bladder fibrosis involves epithelial-to-mesenchymal transition mediated by transforming growth factor-β1.
Am J Physiol Renal Physiol. 2017 Mar 22;:ajprenal.00686.2016
Authors: Wang J, Chen Y, Gu D, Zhang G, Chen J, Zhao J, Wu P
Abstract
Bladder wall fibrosis is a major complication of ketamine-induced cystitis (KC), but the underlying pathogenesis is poorly understood. The aim of the present study was to elucidate the mechanism of ketamine-induced fibrosis in association with epithelial-to-mesenchymal transition (EMT) mediated by transforming growth factor-β1 (TGF-β1). Sprague-Dawley rats were randomly distributed into four groups, which received saline, ketamine, ketamine combined with a TGF-β receptor (TβR) inhibitor (SB505124) for 16 weeks, or 12 weeks of ketamine and 4 weeks of abstinence. In addition, the profibrotic effect of ketamine was confirmed in SV-40 immortalized human uroepithelial (SV-HUC-1) cells. The ketamine-treated rats displayed voiding dysfunction and decreased bladder compliance. Bladder fibrosis was accompanied by the appearance of a certain number of cells expressing both epithelial and mesenchymal markers, indicating that epithelial cells might undergo EMT upon ketamine administration. Meanwhile, the expression level of TGF-β1 was significantly up-regulated in the urothelium of bladders in ketamine-treated rats. Treatment of SV-HUC-1 cells with ketamine increased the expression of TGF-Î...

Source: Am J Physiol Renal P... - March 22, 2017 Category: Urology & Nephrology Authors: Wang J, Chen Y, Gu D, Zhang G, Chen J, Zhao J, Wu P Tags: Am J Physiol Renal Physiol Source Type: research