Transforming growth factor-beta and the pathogenesis of glomerular diseases

Curr Opin Nephrol Hypertens. 1994 Jan;3(1):54-8. doi: 10.1097/00041552-199401000-00007.

Abstract

Transforming growth factor-beta (TGF-beta) is a cytokine that is important in embryogenesis, development, carcinogenesis, and tissue repair. TGF-beta is unique among cytokines in its widespread actions on the regulation of extracellular matrix. In a model of acute mesangial proliferative glomerulonephritis, it was shown that overproduction of TGF-beta is the cause of pathologic matrix accumulation in the nephritic glomeruli. TGF-beta acted to increase matrix production, inhibit matrix degradation, and modulate matrix receptors in the glomerulonephritic rats. Elevated expression of TGF-beta was also found in other experimental glomerular diseases, including diabetic nephropathy. Studies of humans with glomerulonephritis and diabetic nephropathy also strongly implicated TGF-beta in the pathogenesis of glomerular matrix build-up. Recently, the proteoglycan decorin was shown to neutralize TGF-beta. When injected into glomerulonephritic rats, decorin markedly suppressed pathologic matrix deposition in the glomeruli. Thus, decorin offers hope as a treatment for progressive kidney diseases caused by the overproduction of TGF-beta.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • Diabetic Nephropathies / physiopathology
  • Disease Models, Animal
  • Extracellular Matrix / physiology
  • Glomerulonephritis / physiopathology*
  • Glomerulonephritis, Membranoproliferative / physiopathology*
  • Humans
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / physiology
  • Nephritis / physiopathology*
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta / physiology*

Substances

  • Transforming Growth Factor beta