Hepatocyte delivery of miR-34b/c reduces hepatic stellate cell activation and improves liver fibrosis

Liver fibrosis is a major health problem worldwide and currently available treatments are only supportive. The microRNA-34 (miR-34) family is upregulated in response to chronic liver injuries, and miR-34b/c downregulates the platelet-derived growth factor signaling receptors. Mice deleted of miR-34b/c were found to be more susceptible to liver fibrosis. Adeno-associated viral (AAV) vector-mediated hepatocyte-specific expression of miR-34b/c ameliorated liver fibrosis/cirrhosis in mice. Interestingly, expression of miR-34b/c into hepatocytes inhibited hepatic stellate cell activation, although no evidence of miR-34b/c expression or transfer from hepatocytes was found into hepatic stellate cells. In conclusion, these findings support delivery of miR-34b/c as anti-fibrotic treatment and may pave the way toward the development of novel microRNA (miRNA)-based therapies against hepatic fibrosis.