Abstract
Inflammation might be one of the essential underlying mechanisms of renal fibrosis, which is considered a key pathological feature of end-stage renal disease and is closely associated with proteinuria and decreased renal function. Apoptosis-associated speck-like protein containing a CARD (ASC), identified as the central structure of inflammasome, is involved in the progression of interstitial fibrosis; however, its signal transduction pathways remain unclear. In the present study, we performed unilateral ureter obstruction (UUO) in both wild-type and ASC deletion mice to determine the contribution of ASC to renal fibrosis. Compared with control groups, UUO significantly induced renal fibrosis and collagen deposition, as evidenced by photomicrographs. ASC deletion attenuated renal injury, reduced cell infiltration and the release of inflammatory cytokines, protected against apoptosis, and downregulated the PRKR-like endoplasmic reticulum kinase (PERK) pathway of endoplasmic reticulum (ER) stress. Our data identify a novel role of ASC in the regulation of renal fibrosis and ER stress after UUO, strongly indicating that ASC could serve as an attractive target in the treatment of chronic kidney disease.
Highlights
Chronic kidney disease (CKD) is a common concern associated with high mortality and disability worldwide, which leads to much lower quality of life and a substantial economic burden [1, 2]
We focused on the role of ASC in unilateral ureter obstruction- (UUO-) induced renal fibrosis and apoptosis, tried to detect its regulation potential on endoplasmic reticulum (ER) stress or unfolded protein response (UPR)
To determine whether ASC contributes to the progression of renal fibrosis, UUO was performed in both ASC−/− mice and WT mice
Summary
Chronic kidney disease (CKD) is a common concern associated with high mortality and disability worldwide, which leads to much lower quality of life and a substantial economic burden [1, 2]. Interstitial fibrosis contributes to adverse longterm renal prognosis, and inflammation might be one of the essential underlying mechanisms [4]. Inflammatory mediators, such as chemokines or cytokines, interact with myofibroblasts, recruiting more inflammatory cells that migrate into the renal interstitium, thereby causing progressive glomerulosclerosis, mesangial proliferation, and collagen deposition [5]. CKD, the detailed pathways remain to be revealed. Such insights might lead to new therapeutic targets for CKD
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