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MicroRNAs (miRNAs) are a class of ~22-nucleotides noncoding RNAs that regulate gene expression by specifically binding with 3'-untranslated region (3'-UTR) of target gene mRNAs to posttranscriptionally effect mRNA stability and translation,and play essential roles in a variety of biological processes, including cell development, proliferation, differentiation, and apoptosis. Liver fibrosis is the occurrence of liver cell necrosis and inflammatory stimulation, and is characterized by excessive accumulation of extracellular matrices(ECMs). In the fibrotic liver, hepatic stellate cells (HSCs), which are regulated by multiple signal transduction pathways, undergo myofibroblastic transdifferentiation and are generally regarded as the major ECM producer responsible for liver fibrosis. A growing body of evidence suggests that divergent miRNAs participate in liver fibrotic process and activation of HSC. Moreover, members of many signal transduction pathways are important targets for miRNAs. In this review, we make a summary on current understanding of the roles of miRNAs in the development of liver fibrosis, HSC functions and their potential as novel drug targets., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Activation of hepatic stellate cells (HSC) plays a pivotal role in the development of hepatic fibrosis. Transforming growth factor-β1 (TGF-β1) is considered to be the main stimuli factor responsible for the activation of HSC. MicroRNAs (miRNAs) have recently been shown to regulate cell proliferation, differentiation, and apoptosis. The involvement of miRNAs and their roles in TGF-β1-induced HSC activation remains largely unknown. Our study found that the expression of miR-146a was downregulated in HSC in response to TGF-β1 stimulation in dose-dependent manner by one-step real-time quantitative PCR. Moreover, we sought to examine whether miR-146a became dysregulated in CCl(4)-induced hepatic fibrosis in rats. Our study revealed that miR-146a was downregulated in liver fibrotic tissues. In addition, The HSC transfected with miR-146a mimics exhibited attendated TGF-β1-induced α-smooth muscle actin (α-SMA) expression compared with the control. Furthermore, overexpression of miR-146a suppressed TGF-β-induced HSC proliferation, and increased HSC apoptosis. Bioinformatics analyses predict that SMAD4 is the potential target of miR-146a. MiR-146a overexpression in TGF-β1-treated HSC did not decrease target mRNA levels, but significantly reduced target protein expression. These results suggested that miR-146a may function as a novel regulator to modulate HSC activation during TGF-β1 induction by targeting SMAD4., (Copyright © 2012 Elsevier Inc. All rights reserved.)