Physiological roles and pathological involvement of protease activated
receptors in renal diseases: Therapeutic advances and challenges
Abstract
Studies have demonstrated that protease activated receptors (PARs) with
four subtypes (PAR1-4) are mainly expressed in the renal epithelial,
endothelial and podocyte cells. Evidently, the PAR-1 and PAR-2 have
shown differential therapeutic outcomes in rodent models of type-1 and
type-2 diabetic kidney diseases due to distinct etiological basis of
each disease type. Both PAR-1 and PAR-2 blockers/knock-out have
abolished the drug-induced nephrotoxicity in rodents by suppression of
tubular inflammation and fibrosis. Notably, PAR-2 inhibition was found
to improve autophagy in the urethral obstruction model. Only the PAR-1/4
subtypes have emerged as a therapeutic target for the treatment of
experimentally induced nephrotic syndrome where their respective
antibodies attenuated the podocyte apoptosis. So far the PAR-2/PAR-4
subtypes involvement has been tested in sepsis acute kidney injury and
renal ischemia-reperfusion model. This review discusses the existing
gaps, therapeutic advances and future perspectives related to the roles
of different PARs in kidney diseases.