{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:45:06Z","timestamp":1785415506197,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2022-138243OB-I00"],"award-info":[{"award-number":["PID2022-138243OB-I00"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PID2022-138243OB-I00"],"award-info":[{"award-number":["PID2022-138243OB-I00"]}],"id":[{"id":"https:\/\/ror.org\/003x0zc53","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>MicroRNA-122 (miR-122) is the most abundant hepatic microRNA and a key regulator of hepatocyte proliferation, metabolism and differentiation. Although widely studied in hepatocellular carcinoma, its role in liver regeneration remains unexplored. This study investigated how miR-122 deficiency modulates liver regeneration under physiological conditions and during chronic liver injury. A miR-122-deficient mouse model (miR-122\u2212\/\u2212) was generated using CRISPR\/Cas9, and liver regeneration was assessed after two-thirds partial hepatectomy (PHx) in healthy and CCl4-induced fibrotic livers. In healthy liver, miR-122 expression was transiently downregulated within 24 h after PHx, suggesting a physiological role in cell cycle entry. After PHx in non-fibrotic livers, miR-122\u2212\/\u2212 mice showed increased basal proliferation and accelerated regeneration, associated with Cyclin D1 and RhoA overexpression, enhanced cytokinesis and a predominance of diploid hepatocytes. In contrast, miR-122 deficiency markedly exacerbated CCl4-induced fibrosis, leading to cirrhosis-like architecture, impaired hepatocyte function, and severe metabolic dysregulation. Despite increased proliferation after PHx, fibrotic miR-122\u2212\/\u2212 mice exhibited severely impaired regeneration and near-complete mortality. Proteomic analyses revealed metabolic failure, oxidative stress, and inflammatory activation, creating an unfavorable environment for tissue repair. In conclusion, miR-122 plays a dual role in liver regeneration. While its suppression enhances regeneration in healthy liver, loss of miR-122 under fibrotic conditions drives pathological repair, metabolic failure and lethality, highlighting its critical role in chronic liver disease.<\/jats:p>","DOI":"10.3390\/ijms27073149","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:09:18Z","timestamp":1774944558000},"page":"3149","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["miR-122 Deficiency in Mice Enhances Regeneration in Healthy Liver but Drives Pathological Repair and Functional Decline in Fibrotic Liver"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0288-4220","authenticated-orcid":false,"given":"Jordi","family":"Ribera","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Cl\u00ednic of Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0181-9283","authenticated-orcid":false,"given":"Anna","family":"Cardona-Sim\u00f3","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Cl\u00ednic of Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 08036 Barcelona, Spain"},{"name":"Biomedicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, 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Cl\u00ednic of Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 08036 Barcelona, Spain"},{"name":"Department of Fundamental and Clinical Nursing, Faculty of Nursing, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9074-2272","authenticated-orcid":false,"given":"Manuel","family":"Morales-Ruiz","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Cl\u00ednic of Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 08036 Barcelona, Spain"},{"name":"Biomedicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1002\/hep.28988","article-title":"Hepatostat: Liver Regeneration and Normal Liver Tissue Maintenance","volume":"65","author":"Michalopoulos","year":"2017","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/s41580-021-00373-7","article-title":"Liver Regeneration and Inflammation: From Fundamental Science to Clinical Applications","volume":"22","author":"Campana","year":"2021","journal-title":"Nat. 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