Role of TGF-beta in pathogenesis of diabetic nephropathy.

Diabetic nephropathy, a major long-term complication of diabetes mellitus is characterized by hypertrophy of the glomerular and tubuloepithelial structures and thickening of glomerular and tubular basement membranes and progressive accumulation of extracellular matrix proteins (fibronectin, collagens and laminin) in the mesangium and the interstitium. A host of mediators, such as hyperglycemia, glycosylated proteins, systemic and glomerular hypertension, proteinuria, growth factors, and cytokines have been implicated in the pathogenesis of diabetic nephropathy. Of these, the cytokine transforming growth factor (TGF-beta) has emerged as having a key role in the development of renal hypertrophy and accumulation of extracellular matrix in diabetes. TGF-beta is known to have powerful fibrogenic actions resulting from both stimulation of matrix synthesis and inhibition of matrix degradation.