Transforming growth factor-beta and the pathogenesis of glomerular diseases.
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.
University of Utah School of Medicine, Salt Lake City.
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D000818:Animals; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000503:physiopathology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000502:physiology; D005921:Glomerulonephritis / Q000503:physiopathology*; D015432:Glomerulonephritis, Membranoproliferative / Q000503:physiopathology*; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects / Q000502:physiology; D009393:Nephritis / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*
D016212:Transforming Growth Factor beta