The effects of adenosine A2A receptor knockout on renal interstitial fibrosis in a mouse model of unilateral ureteral obstruction

Abstract

Adenosine A2A receptor (A2AR) plays an important regulatory role in the processes of inflammation and fibrosis. However, it is unknown whether A2AR can mediate renal interstitial fibrosis (RIF). To evaluate the effect of genetic A2AR knockout (KO) on the pathological progress of RIF, we applied a unilateral ureteral obstruction (UUO) model of RIF on A2AR KO mice and their wild-type (WT) littermates. Renal pathological assessment was performed at different post-UUO stages using hematoxylin and eosin (H&E) and Masson's trichrome staining as well as quantitative morphological analysis. Our data demonstrated that: (i) the extent of RIF was determined by the development of UUO in a time-dependent manner; (ii) A2AR KO exacerbated the pathological progress of RIF in mice at the early post-UUO stage, i.e. day 3 and day 7; (iii) the profibrotic effect of A2AR KO was prominent until the late post-UUO stage, i.e. day 14, at which RIF reached a similar severity level in A2AR KO and WT mice. Our findings revealed that A2AR KO significantly exacerbated the progression of UUO-induced RIF in mice, prominently at the initial stage.