Claudin-1 is a mediator and therapeutic target in primary sclerosing cholangitis
Primary sclerosing cholangitis (PSC) is a chronic fibrosing cholangiopathy with limited therapeutic options. We identified the cell surface protein Claudin-1 as a key mediator and potential therapeutic target for PSC. In patients, Claudin-1 expression correlates with disease stage and clinical outcomes. Conditional liver epithelial-specific Claudin-1 knockout in mice reduced liver injury, fibrosis, and cholestasis. Monoclonal antibodies targeting Claudin-1 inhibited fibrosis, cholestasis, and the ductular reaction across advanced PSC mouse models by suppressing pro-inflammatory and fibrogenic signaling. These preclinical findings support the clinical development of Claudin-1-specific antibodies for PSC treatment and have significant implications for physicians, researchers, and drug developers in the field of biliary disease.
Authors
- Sai Chung (ORCID: https://orcid.org/0000-0003-2684-7122)
- Julien Moehlin
- Romain Désert (ORCID: https://orcid.org/0000-0001-8786-5741)
- Gary D. Bader (ORCID: https://orcid.org/0000-0003-0185-8861)
- Thomas F. Baumert (ORCID: https://orcid.org/0000-0002-8864-2168)
- Marco Carbone (ORCID: https://orcid.org/0000-0003-4427-0531)
- Punita Dhawan (ORCID: https://orcid.org/0000-0003-3434-8155)
- Angélica T. Vieira (ORCID: https://orcid.org/0000-0002-4556-7671)
- Mathias Heikenwälder (ORCID: https://orcid.org/0000-0002-3135-2274)
- Sheraz Yaqub (ORCID: https://orcid.org/0000-0002-5696-2319)
- Chiara Caime (ORCID: https://orcid.org/0009-0007-2330-3230)
- Olivier Govaere (ORCID: https://orcid.org/0000-0002-4426-6930)
- Laurent Mailly (ORCID: https://orcid.org/0000-0001-6957-7463)
- Cátia T. Perciani (ORCID: https://orcid.org/0000-0003-0377-1778)
- Catherine Schuster (ORCID: https://orcid.org/0000-0001-7281-4511)
- Tom H. Karlsen (ORCID: https://orcid.org/0000-0002-8289-9931)
- Tallulah Andrews (ORCID: https://orcid.org/0000-0003-1120-2196)
- Émilie Crouchet
- Trine Folseraas (ORCID: https://orcid.org/0000-0003-2011-1923)
- Zeina Nehme (ORCID: https://orcid.org/0000-0002-4750-6389)
- Gautam Shankar (ORCID: https://orcid.org/0000-0001-5188-2152)
- Diana Nakib (ORCID: https://orcid.org/0000-0002-4046-2109)
- Roberto Iacone (ORCID: https://orcid.org/0000-0003-3360-3855)
- Tessa Ostyn
- Tania Roskams (ORCID: https://orcid.org/0000-0002-2816-1530)
- Sonya A. MacParland (ORCID: https://orcid.org/0000-0002-8036-1425)
- Ian D. McGilvray (ORCID: https://orcid.org/0000-0003-4649-546X)
- Natascha Roehlen (ORCID: https://orcid.org/0000-0002-6653-8765)
- Mélissa Messé (ORCID: https://orcid.org/0009-0009-2567-9885)
- Jesús M. Bañales (ORCID: https://orcid.org/0000-0002-5224-2373)
- Mark Primeaux (ORCID: https://orcid.org/0000-0001-7589-3745)
- Miki Scaravaglio (ORCID: https://orcid.org/0000-0003-2914-4908)
- Fabio Del Zompo (ORCID: https://orcid.org/0000-0003-3905-9627)
- Geoffrey Teixeira
- Frank Juehling
- Pietro Invernizzi
Institutions
- Oslo University Hospital (NO)
- University Health Network (CA)
- Inserm (FR)
- University of the Basque Country (ES)
- German Cancer Research Center (DE)
- University of Oslo (NO)
- University of Toronto (CA)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
- Norwegian Defence University College (NO)
- University of Nebraska Medical Center (US)
- University of Milano-Bicocca (IT)
- Université de Strasbourg (FR)
- KU Leuven (BE)
Publication Details
- Journal
- Journal of Hepatology
- Published
- 2025-08-20
- DOI
- https://doi.org/10.1016/j.jhep.2025.08.005
- Citations
- 3
- Primary Topic
- Liver Diseases and Immunity
- Type
- article
- Field-Weighted Citation Impact
- 3.97