Abstract
Excessive extracellular matrix accumulation due to chronic liver injury leads to fibrosis, cirrhosis and may then eventually, progress to hepatocellular carcinoma. Small non-coding microRNAs (miRNAs) play important roles in the regulation of multiple liver functions and diseases. Among various miRNAs, miR-221 has recently been reported to be upregulated in liver fibrosis, and its expression correlates with severity of liver fibrosis in HCV patients. We show that downregulation of miR-221 in hepatocytes can ameliorate liver fibrosis by decreasing the activation of HSCs. We inhibited miR-221 expression by an adeno-associated virus encoding a tough decoy against miR-221 (AAV TuD). Reduced levels of serum transaminases and hepatic fibrotic markers were found in mice injected with AAV TuD. Therefore, our findings indicate that suppression of miR-221 in hepatocytes ameliorates liver fibrosis. Our study provides a novel therapeutic approach for the treatment of liver fibrosis via miRNA modulation.
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