Zhang J, Wu J, Gu C, Noble NA, Border WA, Huang Y. Receptor-mediated nonproteolytic activation of prorenin and induction of TGF1 and PAI-1 expression in renal mesangial cells. Am J Physiol Renal Physiol 303: F11–F20, 2012. First published April 25, 2012; doi:10.1152/ajprenal.00050.2012.—While elevated plasma prorenin levels are commonly found in diabetic patients and correlate with diabetic nep...

ACE inhibitors improve endothelial dysfunction, possibly by blocking endothelial angiotensin production. Prorenin, through its binding and activation by endothelial mannose 6-phosphate (M6P) receptors, may contribute to this production. Here, we investigated this possibility as well as prorenin activation kinetics, the nature of the prorenin-activating enzyme, and M6P receptor-independent prore...

In this study, binding properties of human prorenin to rat (pro)renin receptor (r(P)RR) and rat prorenin to human (pro)renin receptor (h(P)RR) were elucidated in vitro to investigate species specificity of prorenin bindings to (P)RR. Both (P)RRs were expressed in vitro based on wheat germ lysate and purified using His trap column. The association and dissociation rate constants of human and rat...

The discovery of the prorenin receptor, now nearly a decade ago, altered our view of the renin-angiotensin system (RAS).1,2 Binding of prorenin, the inactive precursor of renin, to the prorenin receptor results in full catalytic activity of prorenin through a nonproteolytic mechanism that likely involves a conformational change by which the prosegment moves out of the catalytic cleft, which the...

While elevated plasma prorenin levels are commonly found in diabetic patients and correlate with diabetic nephropathy, the pathological role of prorenin, if any, remains unclear. Prorenin binding to the (pro)renin receptor [(p)RR] unmasks prorenin catalytic activity. We asked whether elevated prorenin could be activated at the site of renal mesangial cells (MCs) through receptor binding without...

Prorenin binding to the (pro)renin receptor not only causes a nonproteolytic activation of prorenin leading to the activation of the renin-angiotensin system (RAS), but also stimulates the receptor's own intracellular signaling pathways independent of the RAS. Within the kidneys, the (pro)renin receptor is present in the glomerular mesangium and podocytes, which play an important role in the ma...

Prorenin, the precursor of renin, exists in circulating blood at concentrations that are 5 to 10 higher than those of renin. For many years, prorenin was considered to be an inactive form of renin with no physiological role. Then, in the mid-80s of the last century, Luetscher et al reported that the levels of circulating prorenin (but not renin) are increased in diabetic subjects.1 Subsequent s...

The recently cloned (pro)renin receptor [(P)RR] mediates renin-stimulated cellular effects by activating mitogen-activated protein kinases and promotes nonproteolytic prorenin activation. In vivo, (P)RR is said to be blocked with a peptide consisting of 10 amino acids from the prorenin prosegment called the "handle-region" peptide (HRP). We tested whether human prorenin and renin induce extrace...

PURPOSE A recent study revealed that angiotensin receptor signaling mediates ocular inflammation and neovascularization. It was also found that prorenin undergoes nonproteolytic activation leading to upregulation of the renin-angiotensin system (RAS) when prorenin receptor interacts specifically with the handle region of prorenin. The purpose of the present study was to elucidate the role of th...