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.