Alcohol-related hepatitis induces a specific fibrosis profile through YAP activation in myofibroblasts
Aberrant activation of YAP in hepatocytes contributes to impaired regeneration in alcohol-related hepatitis (AH) by driving their transdifferentiation toward a cholangiocyte-like phenotype. Preliminary data suggest that the extracellular matrix in AH differs from cirrhosis, with an increased laminin-to-fibronectin ratio. In a 3D co-culture model of liver organoids and myofibroblasts, AH organoids increased activation and proliferation of myofibroblasts compared with cirrhosis organoids. Aberrant YAP activation in altered hepatocytes is involved in the activation and proliferation of myofibroblasts in AH livers. Thus, inhibiting YAP in hepatocytes could be an attractive approach for the development of AH treatments to improve hepatic regeneration and decrease fibrogenesis.
Authors
- Alexandre Louvet (ORCID: https://orcid.org/0000-0002-5293-007X)
- Pierre Devaux (ORCID: https://orcid.org/0000-0002-7076-7624)
- Viviane Gnemmi (ORCID: https://orcid.org/0000-0001-7403-4607)
- Cyril Sobolewski (ORCID: https://orcid.org/0000-0002-9404-6290)
- Christian Rolando (ORCID: https://orcid.org/0000-0002-3266-8860)
- Line Carolle Ntandja Wandji (ORCID: https://orcid.org/0000-0002-5517-2286)
- Freddie Bray (ORCID: https://orcid.org/0000-0002-3248-7787)
- Mehdi El Amrani (ORCID: https://orcid.org/0000-0001-9744-7826)
- Laurent Dubuquoy (ORCID: https://orcid.org/0000-0003-3596-5497)
- Emmanuel Boleslawski (ORCID: https://orcid.org/0000-0003-3286-8608)
- Jérôme Eeckhoute (ORCID: https://orcid.org/0000-0002-7222-9264)
- Philippe Mathurin (ORCID: https://orcid.org/0000-0003-3447-2025)
- François Maggiotto
- Solenne Taront
- Mohamed Bou Saleh
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université de Lille (FR)
- Institut Pasteur de Lille (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Miniaturisation pour la Synthèse, l'Analyse et la Protéomique (FR)
- Lille Inflammation Research International Center (FR)
Publication Details
- Journal
- JHEP Reports
- Published
- 2025-08-29
- DOI
- https://doi.org/10.1016/j.jhepr.2025.101580
- Primary Topic
- Alcohol Consumption and Health Effects
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Infrastructures en Biologie Santé et Agronomie
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Association Française pour l'Etude du Foie
- Région Hauts-de-France
- Centre hospitalier régional universitaire de Lille