The (pro)renin receptor and the kidney.
Prorenin binding to the (pro)renin receptor not only causes a nonproteolytic activation of prorenin leading to the activation of the renin-angiotensin system (RAS), but also stimulates the receptor's own intracellular signaling pathways independent of the RAS. Within the kidneys, the (pro)renin receptor is present in the glomerular mesangium and podocytes, which play an important role in the maintenance of the glomerular filtration barrier. Therefore, prorenin-receptor blockers, which competitively bind to the receptor as a decoy peptide, have superior benefits with regard to proteinuria and glomerulosclerosis in experimental animal models with elevated plasma prorenin levels such as diabetes and hypertension compared with conventional RAS inhibitors, possibly by inhibiting both the nonproteolytic activation of prorenin and RAS-independent intracellular signals.
Ichihara
Atsuhiro
A
Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan. atzichi@sc.itc.keio.ac.jp
Kaneshiro
Yuki
Y
Takemitsu
Tomoko
T
Sakoda
Mariyo
M
Itoh
Hiroshi
H
D000818:Animals; D001794:Blood Pressure; D015870:Gene Expression; D006801:Humans; D006977:Hypertension, Renal / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D015398:Signal Transduction; D000093342:Prorenin Receptor
D011956:Receptors, Cell Surface; D012083:Renin; D000093342:Prorenin Receptor