Functional renin receptors in renal mesangial cells

Activation of the renin-angiotensin system (RAS) and generation of angiotensin II (Ang II) play a crucial role in fibrotic renal disease beyond this system's hemodynamic actions. Ang II blockade was a great therapeutic breakthrough for renal and cardiovascular diseases; however, this slows, but does not stop, disease progression. These limitations leave other molecules unopposed to sustain disease progression. One is renin, which is markedly elevated by Ang II blockade. Recently, a new renin receptor was cloned in renal mesangial cells. This receptor acts as a renin/prorenin cofactor on the cell surface, enhancing efficiency of angiotensinogen cleavage by renin and unmasking prorenin catalytic activity. Unexpectedly, the receptor induces angiotensin-independent cellular effects in renal mesangial cells, suggesting that renin has novel receptor-mediated actions that could play a role in renal fibrosis. Proof of this could lead to a pharmacological compound blocking renin/prorenin binding and activity as an alternative or adjunct to classical inhibitors of the RAS.