Drug discovery for overcoming chronic kidney disease (CKD): New therapy for CKD by a (pro)renin-receptor-blocking decoy peptide

Atsuhiro Ichihara, Mariyo Sakoda, Asako Kurauchi-Mito, Tatsuya Narita, Kenichiro Kinouchi, Hiroshi Itoh

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)20-23
Number of pages4
JournalJournal of Pharmacological Sciences
Volume109
Issue number1
DOIs
Publication statusPublished - 2009

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Drug Discovery
Chronic Renal Insufficiency
Renin
Peptides
Therapeutics
Angiotensin II
Hypertension
Enzyme Precursors

Keywords

  • Angiotensin
  • Chronic kidney disease (CKD)
  • Diabetes
  • Hypertension
  • Mitogen-activated protein kinase
  • Renin

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Drug discovery for overcoming chronic kidney disease (CKD) : New therapy for CKD by a (pro)renin-receptor-blocking decoy peptide. / Ichihara, Atsuhiro; Sakoda, Mariyo; Kurauchi-Mito, Asako; Narita, Tatsuya; Kinouchi, Kenichiro; Itoh, Hiroshi.

In: Journal of Pharmacological Sciences, Vol. 109, No. 1, 2009, p. 20-23.

Research output: Contribution to journalArticle

Ichihara, Atsuhiro ; Sakoda, Mariyo ; Kurauchi-Mito, Asako ; Narita, Tatsuya ; Kinouchi, Kenichiro ; Itoh, Hiroshi. / Drug discovery for overcoming chronic kidney disease (CKD) : New therapy for CKD by a (pro)renin-receptor-blocking decoy peptide. In: Journal of Pharmacological Sciences. 2009 ; Vol. 109, No. 1. pp. 20-23.
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