Angiotensin II and growth factors in the pathogenesis of diabetic nephropathy

Kidney Int Suppl. 2002 Dec;(82):S8-11. doi: 10.1046/j.1523-1755.62.s82.3.x.

Abstract

The renin-angiotensin system (RAS) and growth factors mediate structural and functional changes during the course of diabetic nephropathy (DN). Studies in humans and experimental models with DN suggest their involvement in the development and progression of DN. Activation of renal tissue RAS and increased expression of growth factors have been demonstrated at early stages of the disease. Angiotensin II and growth factors alter renal hemodynamics and exert trophic changes in renal cells that eventually result in fibrosis through direct mechanisms or through the release of other mediators. Their effects are likely modulated by metabolic changes including high glucose and free fatty acids. While blockade of the RAS ameliorates DN in humans, such evidence for blockade of growth factors is still lacking. It is likely that susceptibility to the development of DN and therapeutic efficacy are modulated by genetic polymorphisms in components of the RAS and growth factors including their receptors and other target molecules. Approaches to understand the intricate relationship between these systems and the mechanism(s) by which they alter capillary permeability and result in structural changes are areas of fruitful investigation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Angiotensin II / metabolism*
  • Animals
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / physiopathology
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Kidney / metabolism*
  • Kidney / physiopathology
  • Oxidative Stress
  • Renin-Angiotensin System*
  • Signal Transduction

Substances

  • Glycation End Products, Advanced
  • Intercellular Signaling Peptides and Proteins
  • Angiotensin II