Podocytes as a target of prorenin in diabetes

Mariyo Sakoda, Hiroshi Itoh, Atsuhiro Ichihara

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

High plasma prorenin levels predict the onset of microvascular complications, such as albuminuria/proteinuria, in diabetic patients. In diabetic rats with elevated plasma prorenin levels, treatment with HRP, which competitively inhibits the binding of prorenin to the (pro)renin receptor [(P)RR] as a decoy peptide, significantly prevented the development of albuminuria/proteinuria and glomerulosclerosis, suggesting that (P)RR-bound prorenin plays a significant role in the pathogenesis of diabetic nephropathy. Recently, the presence of (P)RR in podocytes, which represent one of the glomerular filtration barriers, has been reported. Although podocytes are subjected to both high glucose levels and mechanical stretching caused by glomerular hyperfiltration under diabetic conditions, the expression of (P)RR is reportedly regulated by high glucose levels in in vitro mesangial cells and the in vivo kidneys of diabetic rats, whereas mechanical stretching is up-regulated by (P)RR expression in human podocytes. In addition, prorenin treatment not only leads to the generation of intracellular angiotensin (Ang)II, but also activates the phosphorylation of ERK via (P)RR in a manner that acts independently of AngII in human podocytes. Thus, the upregulation of prorenin and (P)RR in podocytes as a result of glomerular hyperfiltration might play an important role in the development of albuminuria/proteinuria via the generation of intracellular AngII and the stimulation of (P)RR-dependent intracellular signals. Further inquiry regarding podocyte (P)RR intracellular signal transduction will be needed to develop a new therapeutic approach targeting podocyte (P)RR in patients with diabetic nephropathy.

Original languageEnglish
Pages (from-to)17-21
Number of pages5
JournalCurrent Diabetes Reviews
Volume7
Issue number1
DOIs
Publication statusPublished - 2011 Jan 1
Externally publishedYes

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Keywords

  • (Pro)renin receptor
  • Albuminuria
  • Glomerular filtration barrier
  • Proteinuria
  • Stretching

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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