Abstract
Glomerulosclerosis, interstitial fibrosis, and tubular atrophy occur together with end-stage kidney failure, irrespective of the primary etiology. Transforming growth factor (TGF)-β is a key factor in these alterations either directly, by stimulating synthesis of extracellular matrix components and/or impairing turnover of extracellular matrix, or indirectly, through other profibrogenic factors such as connective tissue growth factor. TGF-β is important for the proliferation of renal interstitial fibroblasts and the epithelial–mesenchymal transition, through which tubular cells acquire fibroblastic properties. In addition, TGF-β can modulate the immune response in inflammatory renal diseases. Many humoral factors induce TGF-β expression in the kidney, chief among them being various members of the renin–angiotensin–aldosterone system. Proof of the concept that TGF-β is the main mediator of renal fibrosis stems originally from experimental and clinical observations in diabetic nephropathy, and more recently from studies of different types of glomerular disease. It has been clearly demonstrated in clinical studies that TGF-β is overproduced in the kidney and is detected in the blood and urine in various renal diseases. This review will highlight some current aspects of the TGF-β signaling axis in diabetic nephropathy and will put the topic into perspective in terms of further experimental and clinical research.