TRANSFORMING GROWTH-FACTOR-BETA AND THE KIDNEY

Transforming growth factor-beta (TGF-beta) belongs to a family of multifunctional cytokines that play important roles in the regulation of development, immune function and tissue repair. Experimental and clinical studies have demonstrated that TGF-beta is a key mediator of fibrogenesis in normal wound healing but also in chronic-progressive tissue fibrosis. TGF-beta induces matrix protein synthesis, decreases matrix protein degradation and contributes to matrix assembly. Studies in several models of acute and chronic glomerulopathies and tubulointerstitial kidney diseases have identified TGF-beta overexpression as a major determinant of tissue scarring. The clinical relevance of these findings has been confirmed by the detection of TGF-beta overexpression in human biopsy tissues from patients with chronic-progressive kidney diseases. TGF-beta expression was closely correlated with the degree of glomerular and tubulointerstitial sclerosis. Recent data suggest that a TGF-beta autoinduction loop and specific TGF-beta/matrix-interactions largely determine whether TGF-beta expression following tissue injury is terminated or not. Thus, antagonists of TGF-beta such as the TGF-beta-neutralizing proteoglycan decorin offer hope as novel treatments to prevent progressive tissue fibrosis in kidney disease and subsequent end-stage renal failure.