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.
Huang
Yufeng
Y
Fibrosis Research Laboratory, Salt Lake City, UT 84108, USA.
Border
Wayne A
WA
Noble
Nancy A
NA
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism / Q000503:physiopathology; D050527:Mesangial Cells / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System; D016212:Transforming Growth Factor beta / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism; D000093342:Prorenin Receptor
D000804:Angiotensin II; D020928:Mitogen-Activated Protein Kinases; D011956:Receptors, Cell Surface; D012083:Renin; D016212:Transforming Growth Factor beta; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor