Activated prorenin as a therapeutic target for diabetic nephropathy

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

High plasma prorenin levels in diabetic patients predict microvascular complications, but the mechanism of the connection between these factors has remained unclear. (Pro)renin receptors were recently found in the human kidney, and their distribution in the kidneys include the mesangium and podocytes. The binding of prorenin to the (pro)renin receptor triggers two major pathways: the angiotensin II-dependent pathway as a result of the conversion of prorenin to the active form of prorenin through a conformational change, and the angiotensin II-independent, (pro)renin-receptor-dependent intracellular mitogen-activated protein kinase pathway. To investigate whether the (pro)renin-receptor-dependent pathways contribute to the pathophysiology of the end-organ damage that occurs in diabetes, the handle region peptide, which binds to the receptor and competitively inhibits prorenin from binding to the receptor, was administered to rats with streptozotocin-induced type I diabetes and to a model of type II diabetes, db/db mice. The handle region peptide significantly inhibited the development of end-organ damage in these diabetic animals, and had a greater benefit than angiotensin-converting enzyme inhibitors in diabetic angiotensin II-type 1a-receptor-deficient mice. In addition, the infusion of the handle region peptide in animals with streptozotocin-induced type I diabetes significantly regressed the nephropathy that had already occurred. These results suggest that prorenin and the (pro)renin receptor play a pivotal role in the pathophysiology of diabetic nephropathy. Receptor-bound prorenin may prove useful as an important therapeutic target for the prevention and regression of end-organ damage in patients with diabetes.

Original languageEnglish
JournalDiabetes Research and Clinical Practice
Volume82
Issue numberSUPPL. 1
DOIs
Publication statusPublished - 2008 Nov 13

Fingerprint

Diabetic Nephropathies
Renin
Therapeutics
Streptozocin
Type 1 Diabetes Mellitus
Angiotensin II
Peptides
Kidney
Podocytes
Angiotensin Type 1 Receptor
Mitogen-Activated Protein Kinases
Angiotensin-Converting Enzyme Inhibitors
Type 2 Diabetes Mellitus
prorenin receptor

Keywords

  • Angiotensin
  • db/db mouse
  • Mitogen-activated protein kinases
  • Non-proteolytic activation
  • Streptozotocin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine
  • Endocrinology

Cite this

Activated prorenin as a therapeutic target for diabetic nephropathy. / Ichihara, Atsuhiro; Sakoda, Mariyo; Mito-Kurauchi, Asako; Itoh, Hiroshi.

In: Diabetes Research and Clinical Practice, Vol. 82, No. SUPPL. 1, 13.11.2008.

Research output: Contribution to journalArticle

Ichihara, Atsuhiro ; Sakoda, Mariyo ; Mito-Kurauchi, Asako ; Itoh, Hiroshi. / Activated prorenin as a therapeutic target for diabetic nephropathy. In: Diabetes Research and Clinical Practice. 2008 ; Vol. 82, No. SUPPL. 1.
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