Drug Discovery for Overcoming Chronic Kidney Disease (CKD) : New Therapy for CKD by a (Pro)Renin-Receptor-Blocking Decoy Peptide
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概要
- 論文の詳細を見る
Discovery of the (pro)renin receptor uncovered a novel function of renin/prorenin as the receptor ligands in addition to the enzyme and its precursor. The bindings of renin and prorenin to the (pro)renin receptor trigger two major pathways: the angiotensin II–dependent pathway as a result of the enzymatic activation of renin/prorenin and the angiotensin II–independent intracellular pathway involving hypertrophic, hyperplastic, and profibrotic signals. A specific blocker of the receptor was discovered through identification of the amino acid sequence of prorenin prosegment that binds to the receptor and leads to non-proteolytic conversion of prorenin to its active form. A peptide containing this sequence was found to block the binding of prorenin to its receptor. Its infusion in animal models of diabetes and low-renin hypertension significantly inhibited the development and progression of nephropathy, but (pro)renin receptor blockade had no benefit in the clipped kidney of 2K1C rats or rat models of high-renin hypertension. Since renin is still active without a (pro)renin receptor, (pro)renin-receptor blockade elicits a maximum benefit under low-renin conditions. Thus, (pro)renin-receptor blockade can be a useful therapy for chronic kidney disease with low renin levels in the plasma.
- 社団法人 日本薬理学会の論文
- 2009-01-20
著者
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ICHIHARA Atsuhiro
Department of Endocrinology & Anti-Aging Medicine, Keio University School of Medicine
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SAKODA Mariyo
Department of Internal Medicine, Keio University School of Medicine
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KURAUCHI MITO
Department of Internal Medicine, Keio University School of Medicine
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NARITA Tatsuya
Department of Internal Medicine, Keio University School of Medicine
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KINOUCHI Kenichiro
Department of Internal Medicine, Keio University School of Medicine
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ITOH Hiroshi
Department of Internal Medicine, Keio University School of Medicine
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Kurauchi-Mito Asako
Departments of Anti-Aging Medicine & Endocrinology and Internal Medicine, Keio University School of
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Kurauchi Mito
Department Of Internal Medicine Keio University School Of Medicine
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Narita Tatsuya
Department Of Internal Medicine Keio University School Of Medicine
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Itoh Hiroshi
Department Of Astronomy Kyoto University
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Sakoda Mariyo
Department Of Internal Medicine Keio University School Of Medicine
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Ichihara Atsuhiro
Department Of Endocrinology & Anti-aging Medicine Keio University School Of Medicine
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Kinouchi Kenichiro
Department Of Internal Medicine Keio University School Of Medicine
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Itoh Hiroshi
Department Of Aeronautics And Astronautics The University Of Tokyo
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Itoh Hiroshi
Department Of Advanced Materials Science Faculty Of Engineering Kagawa University
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