8.1 PAR2 mediates renal tubular epithelial inflammation via inhibition of autophagy
A study has depicted the pathogenic role of PAR2 mediated inflammation using in-vitro cellular models and experimental obstructive renal injury models in mice [1]. In HK-2 cells up-regulation of PAR2 induced a decline in autophagy which promoted renal inflammation. These changes were attenuated by silencing the PAR2 expression which enhanced the autophagy process and subsequently lowered inflammation in these cells. Similar findings were confirmed in experimental unilateral obstructive injury in which higher renal inflammation (IL-1β, TGF-1β, MCP-1, and TNF-α) was observed due to reduced autophagy markers namely (Atgs) autophagy-related genes and (LC3): Microtubule-associated protein 1A/1B-light chain 3 and increased PAR2 protein levels. Further improvement of autophagy by administering mTOR inhibitor rapamycin or PAR2 antagonist attenuated renal inflammation in the UUO model. These outcomes reveal that PAR2 activation during obstructive renal injury reduces the autophagy process and thereby enhances inflammation, cellular and tissue damage.