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Diabetic complications: a role for the prorenin-(pro)renin receptor-TGF-beta1 axis?

Mieke van den Heuvel1, Wendy W Batenburg, A H Jan Danser

  • 1Division of Pharmacology, Vascular and Metabolic Diseases, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.

Molecular and Cellular Endocrinology
|October 9, 2008
PubMed

Insights

Diabetic cardiovascular complications may stem from a discordant renin-angiotensin system (RAS). Targeting the prorenin-(pro)renin receptor-TGF-beta axis could offer new therapeutic strategies for diabetes.

Area of Science:

  • Endocrinology
  • Cardiovascular Medicine
  • Nephrology

Background:

  • Diabetes mellitus is linked to cardiovascular disease, including nephropathy.
  • Endothelial dysfunction, potentially mediated by a discordant tissue renin-angiotensin system (RAS), contributes to diabetic vascular complications.
  • Elevated plasma prorenin in diabetics with microvascular issues suggests a role in discordant RAS, contrasting with low plasma renin levels.

Purpose of the Study:

  • To review the role of the prorenin-(pro)renin receptor-TGF-beta(1) axis in diabetic complications.
  • To explore prorenin's function beyond its precursor role to renin.
  • To identify potential therapeutic targets for reducing diabetes-related morbidity and mortality.

Main Methods:

  • Literature review focusing on the prorenin-(pro)renin receptor-TGF-beta(1) axis.
  • Analysis of existing research on renin-angiotensin system dysregulation in diabetes.
  • Discussion of prorenin's interaction with its receptor and downstream signaling pathways.

Main Results:

  • Prorenin binds to a (pro)renin receptor, activating local angiotensin-dependent and -independent pathways.
  • Prorenin stimulation of the transforming growth factor-beta (TGF-beta) system is implicated in diabetic complications.
  • The discordant RAS, involving prorenin, may mediate endothelial dysfunction in diabetes.

Conclusions:

  • The prorenin-(pro)renin receptor-TGF-beta(1) axis is a significant contributor to diabetic vascular complications.
  • Interference with this pathway represents a promising therapeutic avenue.
  • Targeting this axis may reduce diabetes-related morbidity and mortality.

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