Role of (pro)renin receptor in cardiovascular cells from the aspect of signaling.

The renin-angiotensin-aldosterone system regulates homeostasis of salt and water, vasoconstriction, and remodeling in cardiovascular and renal cells via activation of intracellular signaling pathway. Prorenin, the precursor of renin, had long been considered to be an inactive form. However, a receptor--the (pro)renin receptor--that binds to both renin and prorenin has been recently identified. Prorenin binding to (pro)renin receptors both results in angiotensinogen cleaving into angiotensin (Ang) I, and triggers activation of (pro)renin receptor-stimulated signal transduction pathways, independent of generating Ang II. In the last decade, it has been reported that the intracellular signaling pathway is activated by prorenin in cardiomyocytes, mesangial cells, podocytes, distal tubular cells, vascular endothelial cells and vascular smooth muscle cells, indicating that prorenin mediates intracellular effects in various cardiovascular and kidney cells. In this review, we summarize novel intracellular signaling systems and their downstream effects via (pro)renin receptors in cardiovascular and kidney cells.