Protease‐activated receptor‐1 contributes to renal injury and interstitial fibrosis during chronic obstructive nephropathy

• DOI: 10.1111/jcmm.14028
• Publication Date: 2018-11-28T17:59:13Z
• Authors: Maaike Waasdorp; Dennis M. de Rooij; Sandrine Florquin; JanWillem Duitman; C. Arnold Spek
• Keywords: Mice, Knockout; 0303 health sciences; Epithelial-Mesenchymal Transition; Original Articles; Acute Kidney Injury; Fibrosis; Mice, Inbred C57BL; Transforming Growth Factor beta1; Mice; 03 medical and health sciences; Chronic Disease; Animals; Nephritis, Interstitial; Kidney Diseases; Receptor, PAR-1; Signal Transduction; Ureteral Obstruction

Abstract End‐stage renal disease, the final stage of all chronic kidney disorders, is associated with fibrosis and inevitably leads to failure death. Transition tubular epithelial cells (TECs) into mesenchymal fibroblasts constitutes a proposed mechanism underlying progression here we assessed whether protease‐activated receptor (PAR)‐1, which recently emerged as an inducer epithelial‐to‐mesenchymal transition (EMT), aggravates fibrosis. We show that PAR‐1 activation on TECs reduces expression markers simultaneously induces marker reminiscent EMT. next damage was reduced in PAR‐1‐deficient mice during unilateral ureter obstruction (UUO) develop diminished fibrotic response. Importantly, however, did hardly observe any signs both wild‐type suggesting not due Instead, accumulation macrophages significantly animals were accompanied by production MCP‐1 TGF‐β. Overall, thus drives EMT vitro UUO‐induced although this likely PAR‐1‐dependent pro‐fibrotic cytokine rather than