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2026-03-30

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cc-by (c) Ribera, Jordi et al., 2026
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/229978

Deficiency in Mice Enhances Regeneration in Healthy Liver but Drives Pathological Repair and Functional Decline in Fibrotic Liver

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https://doi.org/10.3390/ijms27073149

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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-/-) 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-/- 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-/- 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.

Matèries

Proliferació cel·lular, Hepatectomia, Malalties del fetge, Regeneració (Biologia)

Matèries (anglès)

Cell proliferation, Hepatectomy, Liver diseases, Regeneration (Biology)

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Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

RIBERA, Jordi, et al. Deficiency in Mice Enhances Regeneration in Healthy Liver but Drives Pathological Repair and Functional Decline in Fibrotic Liver. International Journal of Molecular Sciences. 2026. Vol. 27, num. 7. ISSN 1661-6596. [consulted: 27 of June of 2026]. Available at: https://hdl.handle.net/2445/229978

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