IMR Press / FBL / Volume 13 / Issue 13 / DOI: 10.2741/3057

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
Smad7 as a therapeutic agent for chronic kidney diseases
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1 Department of Medicine, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong

*Author to whom correspondence should be addressed.

 

Front. Biosci. (Landmark Ed) 2008, 13(13), 4984–4992; https://doi.org/10.2741/3057
Published: 1 May 2008
Abstract

Increasing evidence shows that transforming growth factor-β TGF-β1 (TGF-β1) is upregulated and plays a diverse role in renal fibrosis by stimulating extracellular matrix (ECM) production, while inhibiting renal inflammation. Recent studies have identified that TGF-β1, once activated, signals through its downstream signaling pathway to exert its biological effects. It is now well accepted that TGF-β regulates fibrosis positively by receptor-associated Smads including Smad2 and Smad3, but negatively by an inhibitory Smad, called Smad7. We and other investigators have shown that gene transfer of Smad7 is able to inhibit renal fibrosis in a number of experimental models of chronic kidney diseases, including obstructive nephropathy, remnant kidney disease, and autoimmune crescentic glomerulonephritis. Blockade of Smad2/3 activation is a major mechanism by which overexpression of Smad7 inhibits renal scarring. Furthermore, our recent findings also demonstrate that Smad7 plays a critical role in anti-inflammation in chronic kidney diseases by blocking the NF.κB-dependent inflammatory pathway. Thus, Smad7 has a unique role in both anti-renal fibrosis and inflammation. These findings also indicate that targeting the TGF-β/Smad signaling pathway by overexpressing Smad7 may provide a novel, specific, and effective therapy for chronic kidney diseases.

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