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 re...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 reninangiotensin 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.展开更多
Inhibition of the renin angiotensin system has beneficial effects in cardiovascular prevention and treatment. The advent of orally active direct renin inhibitors adds a novel approach to antagonism of the renin-angiot...Inhibition of the renin angiotensin system has beneficial effects in cardiovascular prevention and treatment. The advent of orally active direct renin inhibitors adds a novel approach to antagonism of the renin-angiotensin system.Inhibition of the first and rate-limiting step of the renin angiotensin cascade offers theoretical advantages over downstream blockade.However,the recent discovery of the(pro)renin receptor which binds both renin and prorenin,and which can not only augment catalytic activity of both renin and prorenin in converting angiotensinogen to angiotensinⅠ,but also signal intracellularly via various pathways to modulate gene expression,adds a significant level of complexity to the field.In this review,we will examine the basic and clinical data on renin and its inhibition in the context of cardiovascular pathophysiology.展开更多
The renin-angiotension system (RAS) plays an important role in cardiovascular and renal physiology and diseases. Recent discoveries of prorenin and prorenin receptor add new contents to RAS. Renin and prorenin binding...The renin-angiotension system (RAS) plays an important role in cardiovascular and renal physiology and diseases. Recent discoveries of prorenin and prorenin receptor add new contents to RAS. Renin and prorenin binding to the prorenin receptor not only target and facilitate angiotensin generation but also lead to activation of prorenin receptor signal transduction pathways,which is distinct from classical RAS signaling. In this paper,the construction,function and signal trasduction of prorenin,prorenin receptor and handle region peptide are reviewed.展开更多
The classical renin-angiotensin system（RAS） in the body has been studied intensively in the last decades, since it is known that this system is involved in the regulation of blood pressure. Since nearly all members ...The classical renin-angiotensin system（RAS） in the body has been studied intensively in the last decades, since it is known that this system is involved in the regulation of blood pressure. Since nearly all members of the classical RAS have also been identified within the brain in the last decades and due to the existence of the blood-brain barrier, a RAS within the brain（bRAS） that is largely independent from the peripheral RAS has been postulated. All members of the angiotensin family as e.g., angiotensin II, angiotensin IV and angiotensin II（1-7） along with the respective receptors（e.g., angiotensin II receptor type 1（AT1）, angiotensin II receptor type 2（AT2）, angiotensin IV receptor（AT4）, angiotensin II（1-7） receptor（Mas）） have been identified within the brain. Moreover, a receptor capable of binding renin and the renin precursor prorenin with high affinity has also been detected within the brain. This protein functions as a membrane receptor for（pro）renin and also represents a V-ATPase subunit and is therefore termed（P）RR or Atp6 ap2, respectively. In this review we shed light on the（known as well as putative） roles and functions of Atp6 ap2 in the brain under physiological and pathophysiological conditions.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 reninangiotensin 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.
基金Supported by(in part)a research grant from Novartis Pharmaceuticals to Joseph J
文摘Inhibition of the renin angiotensin system has beneficial effects in cardiovascular prevention and treatment. The advent of orally active direct renin inhibitors adds a novel approach to antagonism of the renin-angiotensin system.Inhibition of the first and rate-limiting step of the renin angiotensin cascade offers theoretical advantages over downstream blockade.However,the recent discovery of the(pro)renin receptor which binds both renin and prorenin,and which can not only augment catalytic activity of both renin and prorenin in converting angiotensinogen to angiotensinⅠ,but also signal intracellularly via various pathways to modulate gene expression,adds a significant level of complexity to the field.In this review,we will examine the basic and clinical data on renin and its inhibition in the context of cardiovascular pathophysiology.
文摘The renin-angiotension system (RAS) plays an important role in cardiovascular and renal physiology and diseases. Recent discoveries of prorenin and prorenin receptor add new contents to RAS. Renin and prorenin binding to the prorenin receptor not only target and facilitate angiotensin generation but also lead to activation of prorenin receptor signal transduction pathways,which is distinct from classical RAS signaling. In this paper,the construction,function and signal trasduction of prorenin,prorenin receptor and handle region peptide are reviewed.
文摘The classical renin-angiotensin system（RAS） in the body has been studied intensively in the last decades, since it is known that this system is involved in the regulation of blood pressure. Since nearly all members of the classical RAS have also been identified within the brain in the last decades and due to the existence of the blood-brain barrier, a RAS within the brain（bRAS） that is largely independent from the peripheral RAS has been postulated. All members of the angiotensin family as e.g., angiotensin II, angiotensin IV and angiotensin II（1-7） along with the respective receptors（e.g., angiotensin II receptor type 1（AT1）, angiotensin II receptor type 2（AT2）, angiotensin IV receptor（AT4）, angiotensin II（1-7） receptor（Mas）） have been identified within the brain. Moreover, a receptor capable of binding renin and the renin precursor prorenin with high affinity has also been detected within the brain. This protein functions as a membrane receptor for（pro）renin and also represents a V-ATPase subunit and is therefore termed（P）RR or Atp6 ap2, respectively. In this review we shed light on the（known as well as putative） roles and functions of Atp6 ap2 in the brain under physiological and pathophysiological conditions.
