The TGF-beta family of proteins has wide effects on nearly every tissue of the body--it is one of the key players in a mammalian development and homeostasis. It also has particular relevance to renal pathophysiology as one of the central mediators of diabetic nephropathy.The TGF-betas are secreted peptides. They interact with receptors (a family of transmembrane serine/threonine kinases) which upon binding leads to activation of a family of proteins known as the Smads, which regulate gene expression.
The evidence that TGF-beta is involved in diabetic nephropathy is abundant. For one, TGF-beta is overexpressed in glomerular and tubulointerstitial compartments in rodent models of diabetes. In addition, TGF-beta stimulation results in a gene expression program that involves key elements of the fibrotic pathway--with fibrosis being the "common final pathway" not only for diabetic nephropathy but other forms of chronic kidney disease as well. Also, treatment of diabetic mice with neutralizing anti-TGF-beta antibodies helps prevent matrix expansion and renal functional decline. Perhaps modification of this pathway might be a good pharmacologic target for preventing progression of CKD in teh future...
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