Fig. 1.

ANG II-dependent and independent pathways for renin signaling. Both renin and prorenin can bind the dimerized (pro)renin receptor [(P)RR], leading to the activation of different signaling pathways. Binding of prorenin to the receptor results in either direct activation of downstream MAP kinases signaling, or in the nonproteolytic activation of prorenin, facilitating the activation of ERK signaling cascades that can also be triggered by renin binding. Activation of these signaling cascades results in actin polymerization and the expression for profibrotic genes, leading to TGF-β, PAI-1, collagen-I, and fibronection synthesis. Binding of renin to the (P)RR also activates an ANG II-dependent pathway leading to the formation of ANG II and the activation of the AT₁ receptor. Activation of both pathways ultimately leads to end-organ damage. Abbreviations: TGF-β, transforming growth factor β; PAI-1, plasminogen-activator inhibitor-1.