Hepatocyte delivery of miR-34b/c reduces hepatic stellate cell activation and improves liver fibrosis
Authors: Pasquale Piccolo, Rosa Ferriero, Claudia Perna, Edoardo Nusco, Marcello Monti, Rossella De Cegli, Anna Barbato, Nicolina Cristina Sorrentino, Maria Teresa Viscomi, Marica Cariello, Antonio Moschetta, Severo Campione, Nicola Brunetti-Pierri.
Year: 2025
Sources: Molecular Therapy Nucleic Acids
Abstract:
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 vector-mediated hepatocyte-specific delivery of miR-34b/c ameliorated liver fibrosis/cirrhosis in mice. Interestingly, delivery of miR-34b/c to 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-based therapies against hepatic fibrosis.
Category: journals