Calcium-sensing receptor activation attenuates collagen expression in renal proximal tubular epithelial cells.

Calcium-sensing receptor activation attenuates collagen expression in renal proximal tubular epithelial cells. Am J Physiol Renal Physiol. 2019 Mar 06;: Authors: Wu M, Feng Y, Ye GX, Han YC, Wang SS, Ni HF, Wang FM, Gao M, Lv LL, Liu BC Abstract Experimental studies showed that pharmacological activation of calcium-sensing receptor (CaSR) attenuated renal fibrosis in some animal models beyond modification of bone and mineral homeostasis; however, its underlying mechanisms remain largely unknown. Since excessive collagen deposition is the key feature of fibrosis, the present study aimed to examine whether CaSR was involved in the regulation of collagen expression in rats with adenine diet (AD)-induced renal fibrosis and in profibrotic TGF-β1-treated renal proximal tubular epithelial cells (PTECs). The results showed that the CaSR agonist cinacalcet significantly attenuated renal collagen accumulation and tubular injury in AD rats. Additionally, the in vitro study showed that profibrotic TGF-β1 significantly increased the expression of collagen and decreased CaSR expression at the mRNA and protein levels in a concentration- and time-dependent manner. Furthermore, the CaSR CRISPR activation plasmid and cinacalcet partially abrogated the up-regulation of collagen induced by TGF-β1 treatment. Blockade of CaSR by the CRISPR/Cas9 KO plasmid or the pharmacological antagonist Calhex231 further enhanced TGF-β1-induced collagen expression. ...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research