Monday, December 1, 2008

TGF-betas & diabetic nephropathy

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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