Renin, prorenin and the kidney: a new chapter in an old saga.
The binding of prorenin to the (pro)renin receptor triggers 2 major pathways: a nonproteolytic conformational change in prorenin to its active form (angiotensin II-dependent pathway) and an intracellular pathway via the (pro)renin receptor itself (angiotensin II-independent pathway). In diabetic animals, an increased plasma prorenin level not only causes the generation of angiotensin II via the angiotensin II-dependent pathway, it also stimulates the transliteration receptors own intracellular signaling pathway in a manner that is independent of the generated angiotensin II. Thus, the administration of a "handle" region peptide (HRP), which acts as a decoy peptide and competitively inhibits the binding of prorenin to the (pro)renin receptor, has a beneficial effect in the kidneys of diabetic animals with low plasma renin levels. However, the benefits of HRP are slightly reduced in animal models of essential hypertension with relatively high plasma renin levels, and these benefits disappear altogether in animal models of hypertension with extremely high plasma renin levels. Thus, in the kidneys of animal models of diabetes and/or hypertension, both renin and prorenin competitively bind to the (pro)renin receptor and contribute to the pathophysiology of nephropathy. Consequently, renin, prorenin and the (pro) renin receptor may be important therapeutic targets for the prevention and regression of nephropathy in patients with diabetes and/or hypertension.
Ichihara
Atsuhiro
A
Departments of Anti-Aging Medicine & Endocrinology, Keio University School of Medicine, Shinjuku-ku, Tokyo - Japan. atzichi@sc.itc.keio.ac.jp
Sakoda
Mariyo
M
Kurauchi-Mito
Asako
A
Kaneshiro
Yuki
Y
Itoh
Hiroshi
H
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000209:etiology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D007511:Ischemia / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply; D007674:Kidney Diseases / Q000209:etiology*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D012083:Renin / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology; D000093342:Prorenin Receptor
D011956:Receptors, Cell Surface; D012083:Renin; D000093342:Prorenin Receptor