Many animal studies have tried to demonstrate a role for (P)RR in hypertension and in tissue damage associated with diabetes, but if they showed that increased (P)RR was found in kidney of diabetic mice associated with glomerulosclerosis and in heart of hypertensive rats associated with cardiac fibrosis, no definite link could be established between elevated (P)RR and cardiovascular and renal pathologies because of the absence of animal models with a tissue-specific (P)RR knock-out and a lack of a (P)RR antagonist.
Therefore, prorenin-receptor blockers, which competitively bind to the receptor as a decoy peptide, have superior benefits with regard to proteinuria and glomerulosclerosis in experimental animal models with elevated plasma prorenin levels such as diabetes and hypertension compared with conventional RAS inhibitors, possibly by inhibiting both the nonproteolytic activation of prorenin and RAS-independent intracellular signals.
This study clearly provided in vivo evidence for the AngII-independent MAPK activation by human (pro)renin receptor and induction of glomerulosclerosis with increased TGF-beta1 expression.