Transforming growth factor- and diabetic nephropathy

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...