Involvement of receptor-bound prorenin in development of nephropathy in diabetic db/db mice

Atsuhiro Ichihara, Mariyo Sakoda, Asako Kurauchi-Mito, Akira Nishiyama, Hiroshi Itoh

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Previous studies have demonstrated that prorenin plays a significant role in the development and progression of nephropathy in streptozotocin-induced diabetic animals, a model for type 1 diabetes, through a (pro)renin receptor-dependent mechanism. However, whether this novel mechanism also contributes to the mechanism of diabetic nephropathy in type 2 diabetes has remained undetermined. In 16-week-old db/db mice, a model for type 2 diabetes, we found a significant degree of glomerulosclerosis, enhanced immunostaining for the active site of renin (representing non-proteolytically activated prorenin), and an increased immunoreactivity to activated extracellular-signal-related protein kinase 1/2 in the kidneys. These changes were blocked by the chronic subcutaneous administration (1 mg/kg/day) of a decoy peptide with the "handle region" structure, which competitively inhibits prorenin binding to a "handle region"-specific binding protein, such as the (pro)renin receptor. The kidneys of db/db mice also contained increased angiotensin (Ang) I and II levels, eliciting significant microalbuminuria. Treatment with the "handle region" peptide significantly decreased the renal content of Ang I and II and inhibited the development of microalbuminuria. Thus prorenin also contributes to the development of nephropathy in type II diabetes, probably through a (pro)renin receptor-dependent mechanism.

Original languageEnglish
Pages (from-to)332-340
Number of pages9
JournalJournal of the American Society of Hypertension
Volume2
Issue number5
DOIs
Publication statusPublished - 2008 Sep 1

Keywords

  • Albuminuria
  • angiotensin
  • glomerulosclerosis
  • type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

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