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 ti...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） constitut-ing the Wnt signaling receptor complex. Here, the roles of PRR in kidney physiology and diabetic conditions as well as recent fndings regarding a soluble form of PRR are discussed. We also propose the possible mechanism concerning diabetic nephropathy as “trade-off hypothe-sis” from a PRR point of view. In brief, under hypergly-cemic conditions, injured podocytes degrade degener-ated 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, interleukin1β, and tumor necrosis factor-α ending in diabetic ne-phropathy progression. Although many fndings led us to better PRR understanding, future works should elu-cidate which PRR functions, of the four discussed here, are dominant in each cell and kidney disease context.展开更多
文摘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） constitut-ing the Wnt signaling receptor complex. Here, the roles of PRR in kidney physiology and diabetic conditions as well as recent fndings regarding a soluble form of PRR are discussed. We also propose the possible mechanism concerning diabetic nephropathy as “trade-off hypothe-sis” from a PRR point of view. In brief, under hypergly-cemic conditions, injured podocytes degrade degener-ated 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, interleukin1β, and tumor necrosis factor-α ending in diabetic ne-phropathy progression. Although many fndings led us to better PRR understanding, future works should elu-cidate which PRR functions, of the four discussed here, are dominant in each cell and kidney disease context.
