Soluble (pro)renin receptor promotes fibrotic response in renal proximal tubule epithelial cells in vitro via Akt/ β-catenin/Snail signaling pathway.

Soluble (pro)renin receptor promotes fibrotic response in renal proximal tubule epithelial cells in vitro via Akt/β-catenin/Snail signaling pathway. Am J Physiol Renal Physiol. 2020 Aug 31;: Authors: Xie S, Su J, Lu A, Lai Y, Mo S, Pu M, Yang T Abstract Tubulointerstitial fibrosis has been regarded as a critical event in the pathogenesis of chronic kidney disease (CKD). Soluble form of PRR (sPRR), generated by site-1 protease (S1P) cleavage of full-length PRR, is detected in biological fluid and elevated under certain pathological conditions. The present study was designed to evaluate the potential role of sPRR in regulation of fibrotic response in cultured human renal proximal tubular cell line human kidney 2 (HK-2) cells, in the setting of TGF-β or sPRR-His treatment. TGF-β induced fibrotic response of HK-2 cells was indicated by the upregulation of fibronectin (FN) expression, meanwhile, TGF-β could also induce the generation of sPRR, due to enhanced cleavage of fPRR. To explore the role of sPRR in fibrotic response of HK-2 cells, we blocked the production of sPRR with a S1P inhibitor PF429242 and found that PF429242 remarkably suppressed TGF-β induced sPRR generation and FN expression in HK-2 cells. Administration of sPRR-His restored PF429242 attenuated FN expression in HK-2 cells, indicating that sPRR could promote TGF-β induced fibrotic response. Furthermore, sPRR-His alone also increased the abundance of FN in HK-2 cell...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research