Cytokines in kidney disease: the role of transforming growth factor-beta.
Cytokines such as transforming growth factor-beta (TGF-beta) are peptide factors that regulate embryogenesis, development, inflammation, tissue repair, and carcinogenesis. Growing evidence indicates that dysregulation of cytokine actions may underlie the pathogenesis of serious autoimmune, degenerative, and fibrotic diseases. Studies in a model of acute mesangial proliferative glomerulonephritis show that overproduction of TGF-beta is the cause of pathologic accumulation of extracellular matrix in the nephritic glomeruli. Transforming growth factor-beta acts to increase matrix production, inhibit matrix degradation, and modulate matrix receptors in the glomerulonephritic rats. It may also play a role in the glomerular matrix build-up that is a central feature of diabetic nephropathy. Elevated expression of TGF-beta mRNA and TGF-beta protein were found in the glomeruli of diabetic rats along with increased levels of proteoglycans and other matrix components that are known to be induced by TGF-beta. The study of human diabetic glomeruli has also showed markedly elevated levels of TGF-beta protein. Glomeruli from normal kidneys and nonprogressive kidney disorders were negative. The striking ability of TGF-beta to cause exuberant matrix formation may be due to the fact that TGF-beta can induce its own production by resident cells at a site of injury. Thus, the potential for TGF-beta to do harm may be due to this autoinduction mechanism whereby TGF-beta expression can become chronic, creating a vicious circle. As the role that TGF-beta plays in chronic fibrotic diseases becomes better understood, it is likely that TGF-beta inhibitors will become important future drugs for treating these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Border
W A
WA
Division of Nephrology, University of Utah School of Medicine, Salt Lake City.
Noble
N A
NA
D000818:Animals; D058575:Decorin; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000628:therapy; D004044:Dietary Proteins / Q000008:administration & dosage; D005109:Extracellular Matrix / Q000473:pathology; D016326:Extracellular Matrix Proteins; D005355:Fibrosis; D005921:Glomerulonephritis / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007684:Kidney Tubules / Q000473:pathology; D011509:Proteoglycans / Q000627:therapeutic use; D051381:Rats; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology
C546878:DCN protein, human; D058575:Decorin; D004044:Dietary Proteins; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D016212:Transforming Growth Factor beta