Published online Nov 6, 2014. doi: 10.5527/wjn.v3.i4.302
Revised: September 14, 2014
Accepted: October 14, 2014
Published online: November 6, 2014
Processing time: 134 Days and 22.6 Hours
Prorenin receptor (PRR) is a multi-functioning protein possessing at least four different roles: (1) working as a receptor for renin and prorenin producing angiotensin I from angiotensinogen thus enhancing the tissue renin-angiotensin system; (2) inducing intracellular signals when a ligand binds to PRR; (3) participating in the functions of vacuolar proton ATPase; and (4) constituting the Wnt signaling receptor complex. Here, the roles of PRR in kidney physiology and diabetic conditions as well as recent findings regarding a soluble form of PRR are discussed. We also propose the possible mechanism concerning diabetic nephropathy as “trade-off hypothesis” from a PRR point of view. In brief, under hyperglycemic conditions, injured podocytes degrade degenerated proteins and intracellular organelles which require V-ATPase and PRR for vesicle internal acidification. Sustained hyperglycemia overproduces PRR molecules, which are transported to the transmembrane and bind to increased serum prorenin in the diabetic condition. This enhances tissue renin-angiotensin system and PRR-mediated mitogen-activated protein kinase signals, resulting in increased injurious molecules such as transforming growth factor-β, cyclooxygenase2, interleukin-1β, and tumor necrosis factor-α ending in diabetic nephropathy progression. Although many findings led us to better PRR understanding, future works should elucidate which PRR functions, of the four discussed here, are dominant in each cell and kidney disease context.
Core tip: Prorenin receptor (PRR) has shown its multi-functionality in at least four different aspects. In this review, the roles of PRR in kidney physiology and diabetic conditions as well as recent findings regarding a soluble form of PRR are discussed. Additionally, we propose the possible mechanism concerning diabetic nephropathy as “trade-off hypothesis” from a PRR point of view.