Brief intro:
- Author: Lingyun Zhou, Chang-Hai Liu, Duoduo Lv, Klarke Michael Sample, Ángela Rojas, Yugu Zhang, Huandi Qiu, Linye He, Li Zheng, Liyu Chen, Binru Cai, Yiguo Hu, Manuel Romero-Gómez
- Journal: Cell Reports
- Doi: https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00228-1?uuid=uuid%3Ac41bdba4-e2a5-46f5-aa90-47ba98d766db#
- Publication Date: 2025 Mar 30
Abstract
Hepatitis B infection can lead to liver fibrosis and hepatocellular carcinoma (HCC). Despite antiviral therapies, some patients still develop HCC. This study investigates hepatitis B virus (HBV)-induced hepatocyte-hepatic stellate cell (HSC) crosstalk and its role in liver fibrosis and HCC. Using MYC-driven liver cancer stem cell organoids, HCC-patient-derived xenograft (PDX) models, and HBV replication models, this study reveals that HBV transcription affected hepatocyte development, activated the DNA repair pathway, and promoted glycolysis. HBV activated nicotinamide phosphoribosyltransferase (NAMPT) through DNA damage receptor ATR. NAMPT-insulin receptor (INSR)-mediated hepatocyte-HSC crosstalk caused HSCs to develop a myofibroblast phenotype and activated telomere maintenance mechanisms via PARP1 multisite lactylation. Inhibition of the ATR-NAMPT-INSR-PARP1 pathway effectively blocks HBV-induced liver fibrosis and HCC progression. Targeting this pathway could be a promising strategy for chronic HBV infection management.
About PackGene
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
