MicroRNAs in TGF-β/Smad-mediated Tissue Fibrosis

Abstract

Fibrosis is a key process leading to the end-stage organ scarring with loss of functions in a number of human diseases, contributes to about 45 % of deaths in the industrialized world. TGF-β signaling is one of the most important pathways for fibrogenesis in the diseased tissues. Increasing evidence shows that Smad3 is an important mediator of TGF-β/Smad signaling which enhances fibrosis by directly regulating the microRNAs (miRNAs) at transcriptional level. Recent studies clearly show an important role of miRNAs in the pathogenesis of tissue fibrosis in response to TGF-β. It has been reported that Smad3 can regulate a number of TGF-β-dependent miRNAs including miR-21, miR-29, miR-200, miR-192, and miR-433 during tissue fibrosis. Targeting these miRNAs have shown to effectively inhibit fibrosis in the heart, liver, lung, and kidney diseases. A better understanding of the underlying mechanism will provide valuable information for the development of effective therapy for fibrotic diseases.