TY - JOUR
T1 - The renin-angiotensin system, adrenomedullins and urotensin II in the kidney
T2 - Possible renoprotection via the kidney peptide systems
AU - Takahashi, Kazuhiro
AU - Hirose, Takuo
AU - Mori, Nobuyoshi
AU - Morimoto, Ryo
AU - Kozuki, Masahiro
AU - Imai, Yutaka
AU - Totsune, Kazuhito
N1 - Funding Information:
The authors are very grateful to our following collaborators: Dr. Osamu Murakami, Dr. Fumitoshi Satoh, Prof. Sadayoshi Ito, Prof. Takashi Suzuki, and Prof. Hironobu Sasano (Departments of Medicine and Pathology, Tohoku University Graduate School of Medicine, Sendai Japan). This study was supported partly by Tohoku University 21st COE Program Comprehensive Research and Education Center for Planning of Drug Development and Clinical Evaluation (CRESCENDO), by Grants-in-aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan, by a Research Grant from the Takeda Science Foundation (2005), and by the Salt Science Research Foundation, No. 0910 (2009).
PY - 2009/8
Y1 - 2009/8
N2 - The incidence of chronic kidney disease, such as diabetic nephropathy, is increasing throughout the world. Many biologically active peptides play important roles in the kidney. The classical example is the renin-angiotensin system (RAS). Angiotensin II plays critical roles in the progression of chronic kidney disease through its vasoconstrictor action, stimulatory action on cell proliferation, and reactive oxygen-generating activity. A renin inhibitor, aliskiren, has recently been shown to be a clinically effective drug to reduce proteinuria in patients with diabetic nephropathy. (Pro)renin receptor, a specific receptor for renin and prorenin, was newly identified as a member of the RAS. When bound to prorenin, (pro)renin receptor activates the angiotensin I-generating activity of prorenin in the absence of cleavage of the prosegment, and directly stimulates the pathway of mitogen-activated protein kinase independently from the RAS. The kidney peptides that antagonize the intrarenal RAS may have renoprotective actions. Adrenomedullins, potent vasodilator peptides, have been shown to have renoprotective actions. On the other hand, urotensin II, a potent vasoconstrictor peptide, may promote the renal dysfunction in chronic kidney disease together with the renal RAS. Thus, in addition to the renin inhibitor and (pro)renin receptor, adrenomedullins and urotensin II may be novel targets to develop therapeutic strategies against chronic kidney disease.
AB - The incidence of chronic kidney disease, such as diabetic nephropathy, is increasing throughout the world. Many biologically active peptides play important roles in the kidney. The classical example is the renin-angiotensin system (RAS). Angiotensin II plays critical roles in the progression of chronic kidney disease through its vasoconstrictor action, stimulatory action on cell proliferation, and reactive oxygen-generating activity. A renin inhibitor, aliskiren, has recently been shown to be a clinically effective drug to reduce proteinuria in patients with diabetic nephropathy. (Pro)renin receptor, a specific receptor for renin and prorenin, was newly identified as a member of the RAS. When bound to prorenin, (pro)renin receptor activates the angiotensin I-generating activity of prorenin in the absence of cleavage of the prosegment, and directly stimulates the pathway of mitogen-activated protein kinase independently from the RAS. The kidney peptides that antagonize the intrarenal RAS may have renoprotective actions. Adrenomedullins, potent vasodilator peptides, have been shown to have renoprotective actions. On the other hand, urotensin II, a potent vasoconstrictor peptide, may promote the renal dysfunction in chronic kidney disease together with the renal RAS. Thus, in addition to the renin inhibitor and (pro)renin receptor, adrenomedullins and urotensin II may be novel targets to develop therapeutic strategies against chronic kidney disease.
KW - Adrenomedullin
KW - Angiotensin
KW - Prorenin receptor
KW - Urotensin
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U2 - 10.1016/j.peptides.2009.05.018
DO - 10.1016/j.peptides.2009.05.018
M3 - Review article
C2 - 19477209
AN - SCOPUS:67650500280
VL - 30
SP - 1575
EP - 1585
JO - Peptides
JF - Peptides
SN - 0196-9781
IS - 8
ER -