{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:23:54Z","timestamp":1787027034856,"version":"build-2736575974"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Hepatic fibrosis is a progressive pathological condition characterized by chronic inflammation and excessive extracellular matrix deposition (ECM), which may progress to cirrhosis and liver failure. Although specialized pro-resolving lipid mediators have emerged as potential therapeutic agents, their role in advanced hepatic fibrosis remains incompletely defined. This study aimed to determine whether Maresin 1 (MaR1), an endogenous pro-resolving lipid mediator, promotes the resolution of hepatic fibrosis and modulates the associated inflammatory response. Hepatic fibrosis was induced in mice and rats using diethylnitrosamine (DEN). Animals were subsequently treated with MaR1 or vehicle. Histological and biochemical parameters, apoptosis and proliferation markers, and immune profiles associated with hepatic macrophages polarization were assessed. Additionally, the expression and subcellular localization of retinoic acid related orphan receptor alpha (ROR\u03b1) and nuclear factor kappa B (NF-\u03baB p65) were analysed. MaR1 treatment significantly attenuated hepatic fibrosis, reduced the ECM accumulation, and promoted restoration of liver parenchyma, accompanied by decreased hepatocellular injury and enhanced regenerative capacity. MaR1 also induced immune reprogramming, favouring anti-inflammatory and homeostatic macrophage phenotypes. These effects were associated with increased nuclear activation of ROR\u03b1 and modulation of NF-\u03baB signalling pathways. These findings demonstrate that MaR1 promotes the resolution of hepatic fibrosis through macrophage polarization and modulation of the ROR\u03b1\/NF-\u03baB axis. This study advances the understanding of pro-resolving mechanisms in hepatic fibrosis and positions MaR1 as a pharmacologically relevant candidate for the development of targeted antifibrotic therapies in chronic liver disease.<\/jats:p>","DOI":"10.3389\/fphar.2026.1826739","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T08:29:41Z","timestamp":1777278581000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Maresin 1 induces resolution of hepatic fibrosis through ROR\u03b1-dependent reprogramming of resident macrophages"],"prefix":"10.3389","volume":"17","author":[{"given":"Francisca","family":"Herrera Vielma","sequence":"first","affiliation":[{"name":"Pharmacology Laboratory, Biomedical Sciences Department, Faculty of Health Sciences, University of Talca","place":["Talca, Chile"]},{"name":"Institute of Chemistry of Natural Resources, University of Talca","place":["Talca, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mat\u00edas","family":"Qui\u00f1ones San Martin","sequence":"additional","affiliation":[{"name":"Pharmacology Laboratory, Biomedical Sciences Department, Faculty of Health Sciences, University of Talca","place":["Talca, Chile"]},{"name":"Institute of Chemistry of Natural Resources, University of Talca","place":["Talca, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00e1s","family":"Mu\u00f1oz-Carrasco","sequence":"additional","affiliation":[{"name":"Pharmacology Laboratory, Biomedical Sciences Department, Faculty of Health Sciences, University of Talca","place":["Talca, Chile"]},{"name":"School of Biotechnology Engineering, Faculty of Agricultural and Forestry Sciences, Catholic University of Maule","place":["Talca, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Berrocal-Navarrete","sequence":"additional","affiliation":[{"name":"Pharmacology Laboratory, Biomedical Sciences Department, Faculty of Health Sciences, University of Talca","place":["Talca, Chile"]},{"name":"Faculty of Health Sciences, University of Talca","place":["Talca, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s A.","family":"Herrada","sequence":"additional","affiliation":[{"name":"Lymphatic Vasculature and Inflammation Research Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de Concepci\u00f3n","place":["Concepci\u00f3n, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Olate-Briones","sequence":"additional","affiliation":[{"name":"Lymphatic Vasculature and Inflammation Research Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de Concepci\u00f3n","place":["Concepci\u00f3n, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e1n","family":"Zagmutt","sequence":"additional","affiliation":[{"name":"Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya","place":["Sant Cugat del Vall\u00e8s, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosal\u00eda","family":"Rodr\u00edguez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya","place":["Sant Cugat del Vall\u00e8s, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Pharmacology Laboratory, Biomedical Sciences Department, Faculty of Health Sciences, University of Talca","place":["Talca, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Z\u00fa\u00f1iga-Hernandez","sequence":"additional","affiliation":[{"name":"Pharmacology Laboratory, Biomedical Sciences Department, Faculty of Health Sciences, University of Talca","place":["Talca, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"48","DOI":"10.5604\/16652681.1226814","article-title":"Management strategies for liver fibrosis","volume":"16","author":"Altamirano-Barrera","year":"2017","journal-title":"Ann. 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