title: Transforming growth factor-beta and angiotensin II: the missing link from glomerular hyperfiltration to glomerulosclerosis?
abstract: Both angiotensin II and TGF-beta are key mediators of glomerular and tubulointerstitial injury and fibrosis in progressive kidney diseases. It was thought that angiotensin II damages the kidney by increasing glomerular filtration pressure, whereas autocrine TGF-beta overexpression occurs from unidentified mechanisms. Recent studies reveal that angiotensin II is a potent inducer of TGF-beta synthesis in a variety of cells and that this mechanism exerts important biological effects including extracellular matrix accumulation, cell proliferation, and hypertrophy. Because these studies were performed in vitro, there is clear evidence that the biological effects were observed independently of the vasoconstrictive properties of angiotensin II. Although it is difficult to study angiotensin II-mediated effects in vivo without influencing systemic and glomerular blood pressure, further studies are needed to evaluate the ability of ACE-inhibitors and angiotensin II receptor blockers to suppress TGF-beta overexpression in selected models of chronic progressive kidney disease.
authors.affiliation: Division of Nephrology and Hypertension, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ketteler
authors.forename: N A
authors.initials: NA
authors.lastname: Noble
authors.forename: W A
authors.initials: WA
authors.lastname: Border
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D005919:Glomerular Filtration Rate / Q000502:physiology; D005920:Glomerular Mesangium / Q000378:metabolism; D005921:Glomerulonephritis / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000503:physiopathology*; D012084:Renin-Angiotensin System / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D016212:Transforming Growth Factor beta; D000804:Angiotensin II