OBJECTIVE The term "receptor-associated prorenin system" (RAPS) refers to the pathogenic mechanisms whereby prorenin binding to its receptor dually activates the tissue renin-angiotensin system (RAS) and RAS-independent intracellular signaling via the receptor. The aim of the present study was to define the association of the RAPS with diabetes-induced retinal inflammation. RESEARCH DESIGN AN...

Cardiomyocytes bind, internalize, and activate prorenin, the inactive precursor of renin, via a mannose 6-phosphate receptor (M6PR)--dependent mechanism. M6PRs couple directly to G-proteins. To investigate whether prorenin binding to cardiomyocytes elicits a response, and if so, whether this response depends on angiotensin (Ang) II, we incubated neonatal rat cardiomyocytes with 2 nmol/L proreni...

The mechanism of activation of local renal renin-angiotensin system (RAS) has not been clarified in diabetes mellitus (DM). We hypothesized that the local renal RAS will be activated via increased glomerular filtration and tubular uptake of prorenin and angiotensinogen in diabetic kidney with microalbuminuria. Streptozotocin (STZ)-induced DM and control rats were injected with human prorenin an...

In addition to its well-known role in regulating blood pressure and fluid balance, the renin-angiotensin-aldosterone system (RAAS) has continued to fascinate both researchers and clinicians because of the several additional functions that it has been proposed to carry out. Disruption of the production or action of angiotensin II (Ang II) during development, either by gene mutation or by pharmac...

In addition to its well-known role in regulating blood pressure and fluid balance, the renin-angiotensin-aldosterone system (RAAS) has continued to fascinate both researchers and clinicians because of the several additional functions that it has been proposed to carry out. Disruption of the production or action of angiotensin II (Ang II) during development, either by gene mutation or by pharmac...

Thirteen years ago, Véniant et al1 made the intriguing observation that targeted expression of rat prorenin to the liver under the control of the human 1-antitrypsin promoter increased plasma prorenin levels 600-fold in male transgenic rats and caused cardiac hypertrophy, myocardial fibrosis, and severe renal lesions by 20 weeks of age. Renal renin content in these rats decreased, and plasma an...

Thirteen years ago, Véniant et al1 made the intriguing observation that targeted expression of rat prorenin to the liver under the control of the human 1-antitrypsin promoter increased plasma prorenin levels 600-fold in male transgenic rats and caused cardiac hypertrophy, myocardial fibrosis, and severe renal lesions by 20 weeks of age. Renal renin content in these rats decreased, and plasma an...

Prorenin, the inactive precursor of renin has been suggested to be an indicator of diabetic complications including retinopathy. This concept was originally based on findings that prorenin is elevated in the plasma and vitreous of patients with diabetic retinopathy. Experimental studies in animal models of diabetic retinopathy and retinopathy of prematurity, have confirmed these reports and loc...

The aim of this study was to explore the effects of the renin inhibitor aliskiren in streptozotocin-diabetic TG(mRen-2)27 rats. Furthermore, we investigated in vitro the effect of aliskiren on the interactions between renin and the (pro)renin receptor and between aliskiren and prorenin. Aliskiren distributed extensively to the kidneys of normotensive (non)diabetic rats, localizing in the glomer...

The (pro)renin receptor [(P)RR] is crucial for cardio-renal pathophysiology. The distinct molecular mechanisms of this receptor are still incompletely understood. The (P)RR is able to interact with different signalling proteins such as promyelocytic leukemia zinc finger protein (PLZF) and Wnt receptors. Moreover, domains of the (P)RR are essential for V-ATPase activity. V-ATPase- and Wnt-mediat...