TGF-betas & diabetic nephropathy

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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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