Angiotensin II and growth factors in the pathogenesis of diabetic nephropathy.
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.
Rincon-Choles
Hernan
H
Division of Nephrology, Department of Medicine, The South Texas Veterans Health Care System (Audie L. Murphy Division) and The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA. choles@uthscsa.edu
Kasinath
Balakuntalam S
BS
Gorin
Yves
Y
Abboud
Hanna E
HE
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress; D012084:Renin-Angiotensin System; D015398:Signal Transduction
D017127:Glycation End Products, Advanced; D036341:Intercellular Signaling Peptides and Proteins; D000804:Angiotensin II