Distinct roles of Smads and microRNAs in TGF-β signaling during kidney diseases

Publication date: April 2013 Source:Hong Kong Journal of Nephrology, Volume 15, Issue 1 Author(s): Rong Li , Hui Y. Lan , Arthur C.K. Chung Chronic kidney disease (CKD) is known to be the hallmark with fibrosis and inflammation that leads to end stage renal disease. Since the discovery over 2 decades ago of transforming growth factor (TGF)-β as a key mediator in CKD, studies of TGF-β signaling in the kidney have focused on fibrosis and inflammation. TGF-β exerts its cellular effect via Smad2 and Smad3 after binding to its receptors. Smad7, as an inhibitory Smad, provides a negative feedback loop to limit TGF-β action for maintaining homeostasis. Recently, the precise roles of individual Smads and receptors have been further characterized and the results reveal the complexity of TGF-β signaling during CKD. Although Smad3 plays a pathogenic role in CKD, Smad2 and Smad7 are protective. Furthermore, Smad4 enhances Smad3-mediated renal fibrosis as well as suppresses nuclear factor–κB-driven renal inflammation in a Smad7-dependent manner. Emerging evidence demonstrates the ability of TGF-β/Smad3 signaling to regulate specific microRNAs, revealing that microRNAs are critical downstream effectors of TGF-β/Smad3 signaling in renal fibrosis and inflammation. Recent studies in animal models of kidney disease demonstrate the therapeutic potential of microRNA therapy, Smad3 inhibitor, and Smad7 agonist in CKD. Because the accumulation of extracellular matrix and infiltrat...
Source: Hong Kong Journal of Nephrology - Category: Urology & Nephrology Source Type: research