{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:14:54Z","timestamp":1783523694562,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Exosomes derived from hepatitis B virus (HBV)\u2010infected hepatocytes (HBV\u2010Exo) promote liver fibrosis. Emerging evidence implicates METTL3 and P2RX7 as critical drivers of liver fibrosis. However, the molecular mechanisms by which HBV\u2010Exo drive hepatic fibrosis remain poorly understood. This study investigated the mechanistic involvement of METTL3 and P2RX7 in this fibrotic process. Exosomes from pHBV1.3\u2010transfected, HBV\u2010replicating THLE\u20102 hepatocytes (HBV\u2010THLE\u20102\u2010Exo) were isolated and used to incubate LX\u20102 hepatic stellate cells (HSCs). Impacts on LX\u20102 cells were evaluated by detecting cell viability, proliferation, invasion, migration, and fibrosis marker expression. MeRIP, RIP, RNA pull\u2010down, and mRNA stability assays were used to assess the METTL3\/P2RX7 mRNA interaction. A CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced mouse model of liver fibrosis was generated to elucidate the role in vivo. HBV\u2010THLE\u20102\u2010Exo elevated METTL3 levels in recipient LX\u20102 HSCs. HBV\u2010THLE\u20102\u2010Exo enhanced the proliferation, invasion, migration, and fibrosis marker expression in LX\u20102 HSCs in vitro. Moreover, METTL3\u2010depleted exosomes (si\u2010METTL3\u2010HBV\u2010THLE\u20102\u2010Exo) attenuated LX\u20102 cell proliferation, invasion, migration, and expression of fibrotic markers compared to HBV\u2010THLE\u20102\u2010Exo. Mechanistically, METTL3 stabilized P2RX7 in an IGF2BP1\u2010m6A\u2010dependent manner. P2RX7 overexpression reversed si\u2010METTL3\u2010HBV\u2010THLE\u20102\u2010Exo\u2010mediated alterations in LX\u20102 cell proliferation, invasion, migration, and fibrosis marker expression in vitro. Additionally, HBV\u2010THLE\u20102\u2010Exo exacerbated liver fibrosis in CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced mice. Our findings unveil a novel METTL3\/P2RX7 axis by which HBV\u2010Exo drive HSC activation and liver fibrosis. These findings elucidate a novel exosome\u2010mediated regulatory axis in liver fibrosis, suggesting the therapeutic potential of targeting METTL3\/P2RX7 axis.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70645","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:24:47Z","timestamp":1765977887000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exosomes From Hepatitis B Virus\u2010Infected Hepatocytes Induce Liver Fibrosis Through METTL3\u2010Mediated m6A Modification of P2RX7 mRNA"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6095-5832","authenticated-orcid":false,"given":"Caixia","family":"Li","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Hospital of NanHai Economic Development Zone Foshan Guangdong 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