Renin receptor blockade: a better strategy for renal protection than renin-angiotensin system inhibition?
Prorenin and renin bind to a 350-amino acid protein called the (pro)renin receptor, which is present on the surface and functions intracellularly. When the receptor's N terminus binds either prorenin or renin, intracellular signaling occurs via extracellular-regulated kinases, which can result in plasminogen activator inhibitor and transforming growth factor-beta production. Investigators have developed a novel decoy peptide, called the handle-region peptide (HRP), which obviates binding of prorenin to the receptor. HRP has successfully inhibited diabetic nephropathy in rats and in angiotensin receptor-deleted mice, and has blocked fibrosis in the hearts of spontaneously hypertensive rats. The same researchers developed a transgenic (pro)renin receptor-expressing rat with glomerulosclerosis that responded dramatically to HRP treatment. However, groups in Paris, Rotterdam, and Berlin have not been able to confirm the findings, and the precise role of the (pro)renin receptor remains imperfectly defined.
Müller
Dominik N
DN
Max Delbrück Center, Experimental and Clinical Research Center, Building 84, Robert-Rössle Strasse 10, 13125 Berlin, Germany.
Luft
Friedrich C
FC
D000959:Antihypertensive Agents / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology* / Q000517:prevention & control; D011956:Receptors, Cell Surface / Q000187:drug effects*; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000517:prevention & control*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D015398:Signal Transduction; D000093342:Prorenin Receptor; D000092502:Renin Inhibitors
D000959:Antihypertensive Agents; D011956:Receptors, Cell Surface; D000093342:Prorenin Receptor; D000092502:Renin Inhibitors
Hypertension. 2006 May;47(5):894-900
16585419
J Am Soc Nephrol. 2006 Sep;17(9):2495-503
16885412
Hypertension. 2005 Nov;46(5):1069-76
16186442
J Am Soc Nephrol. 2007 Jun;18(6):1789-95
17494887
J Clin Invest. 2004 Oct;114(8):1128-35
15489960
J Am Soc Nephrol. 2006 Jul;17(7):1950-61
16738017
Kidney Int. 2006 Jan;69(1):105-13
16374430
J Clin Invest. 2002 Jun;109(11):1417-27
12045255
J Biol Chem. 1998 May 1;273(18):10939-47
9556572
Front Biosci. 2007 Sep 01;12:4810-7
17569611
J Am Soc Nephrol. 2007 Jul;18(7):2054-61
17538189
J Am Soc Nephrol. 2008 Apr;19(4):743-8
18235083
Nat Rev Mol Cell Biol. 2002 Feb;3(2):94-103
11836511
N Engl J Med. 1990 Oct 18;323(16):1101-6
2215578
J Clin Endocrinol Metab. 1975 Jun;40(6):1078-84
166087
N Engl J Med. 1985 May 30;312(22):1412-7
3887168
Hypertension. 2008 Mar;51(3):676-81
18212268
J Biol Chem. 2003 Jun 20;278(25):22217-22
12684512
J Hypertens. 2007 Dec;25(12):2441-53
17984666
Hypertension. 2008 Mar;51(3):682-8
18212269
Kidney Int. 2007 Jul;72(1):45-52
17396111
Hypertens Res. 2007 Nov;30(11):1139-46
18250563
J Clin Invest. 1996 Nov 1;98(9):1966-70
8903314