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<i>,</i> 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.
Authors
- Edoardo Nusco
- Antonio Moschetta (ORCID: https://orcid.org/0000-0003-2123-6074)
- Claudia Perna
- M. Monti (ORCID: https://orcid.org/0000-0003-2983-1716)
- Nicolina Cristina Sorrentino (ORCID: https://orcid.org/0000-0002-3426-5109)
- Nicola Brunetti‐Pierri (ORCID: https://orcid.org/0000-0002-6895-8819)
- Pasquale Piccolo (ORCID: https://orcid.org/0000-0002-8614-2581)
- Severo Campione (ORCID: https://orcid.org/0000-0001-8414-8333)
- Anna Barbato (ORCID: https://orcid.org/0000-0002-5706-7244)
- Rossella De Cegli (ORCID: https://orcid.org/0000-0002-8526-8692)
- Marica Cariello
- Rosa Ferriero (ORCID: https://orcid.org/0000-0001-5090-6087)
- Maria Teresa Viscomi (ORCID: https://orcid.org/0000-0002-9096-4967)
Institutions
- Università Cattolica del Sacro Cuore (IT)
- Agostino Gemelli University Polyclinic (IT)
- Ospedale Antonio Cardarelli (IT)
- Fatebenefratelli Hospital (IT)
- Institute for Experimental Endocrinology and Oncology (IT)
- Scuola Superiore Meridionale (IT)
- Telethon Institute Of Genetics And Medicine (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- University of Bari Aldo Moro (IT)
- University of Naples Federico II (IT)
Publication Details
- Journal
- Molecular Therapy — Nucleic Acids
- Published
- 2025-06-09
- DOI
- https://doi.org/10.1016/j.omtn.2025.102593
- Citations
- 1
- Primary Topic
- Liver physiology and pathology
- Type
- article
- Field-Weighted Citation Impact
- 1.32
Funders
- Alpha-1 Foundation
- PSC Partners Seeking a Cure
- Polo delle Scienze e delle Tecnologie per la Vita, Università degli Studi di Napoli Federico II
- Alpha Foundation for the Improvement of Mine Safety and Health
- European Commission
- Fondazione Telethon
- FP7 Coordination of Research Activities