Targeting the liver clock improves fibrosis by restoring TGF-β signaling
Liver fibrosis due to metabolic diseases is a global health challenge. Many liver functions are rhythmic throughout the day, being controlled by the circadian clock (CC). Here we demonstrate that regulation of the CC is perturbed upon chronic liver injury and this perturbation contributes to fibrotic disease. By showing that a compound targeting the CC improves liver fibrosis in patient-derived models, this study provides a novel therapeutic candidate strategy to treat fibrosis in patients. Additional studies will be needed for clinical translation. Since the findings uncover a previously undiscovered profibrotic mechanism and therapeutic target, the study is of interest for scientists investigating liver disease, clinical hepatologists and drug developers.
Authors
- Clara Ponsolles (ORCID: https://orcid.org/0009-0000-6711-4238)
- Julien Moehlin
- Thomas F. Baumert (ORCID: https://orcid.org/0000-0002-8864-2168)
- Frank Jühling (ORCID: https://orcid.org/0000-0001-6373-2485)
- Mathias Heikenwälder (ORCID: https://orcid.org/0000-0002-3135-2274)
- Kazuaki Chayama (ORCID: https://orcid.org/0000-0002-5530-5341)
- Atish Mukherji (ORCID: https://orcid.org/0000-0002-4273-4200)
- Mayssa Dachraoui
- Lucas L. Geyer
- Mihaela Onea
- Hiroshi Aikata (ORCID: https://orcid.org/0000-0002-3409-2156)
- Catherine Schuster (ORCID: https://orcid.org/0000-0001-7281-4511)
- Cloé Gadenne
- Émilie Crouchet
- Emanuele Felli (ORCID: https://orcid.org/0000-0002-6510-1457)
- Hiromi Abe‐Chayama (ORCID: https://orcid.org/0000-0002-7665-900X)
- Romain Martin
- Marine A. Oudot (ORCID: https://orcid.org/0000-0001-7393-4697)
- Joachim Lupberger (ORCID: https://orcid.org/0000-0003-3996-3907)
- Laura Heydmann (ORCID: https://orcid.org/0000-0002-2273-2267)
- Thibaut Wolf (ORCID: https://orcid.org/0000-0003-0819-1609)
- Patrick Pessaux (ORCID: https://orcid.org/0000-0001-5635-7437)
- Sarah Durand
- Natascha Roehlen (ORCID: https://orcid.org/0000-0002-6653-8765)
- Antonio Saviano (ORCID: https://orcid.org/0000-0001-7585-472X)
- Danijela Heide
- Pierre Chambon (ORCID: https://orcid.org/0000-0002-7861-6046)
- Nicolas Brignon
- Fabio Del Zompo (ORCID: https://orcid.org/0000-0003-3905-9627)
- Yuji Teraoka
Institutions
- Hiroshima University (JP)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- University of Freiburg (DE)
- German Cancer Research Center (DE)
- Institut Universitaire de France (FR)
- Collège de France (FR)
- Heidelberg University (DE)
- University Medical Center Freiburg (DE)
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- Hiroshima Prefectural Hospital (JP)
- Hôpitaux Universitaires de Strasbourg (FR)
- RIKEN Center for Integrative Medical Sciences (JP)
- Kure Medical Center (JP)
- Institute for Translational Medicine and Liver Disease (FR)
- Université de Strasbourg (FR)
- University of Tübingen (DE)
Publication Details
- Journal
- Journal of Hepatology
- Published
- 2024-08-22
- DOI
- https://doi.org/10.1016/j.jhep.2024.07.034
- Citations
- 37
- Primary Topic
- Digestive system and related health
- Type
- article
- Field-Weighted Citation Impact
- 20.36
Funders
- Styrelsen för Internationellt Utvecklingssamarbete
- Deutsches Krebsforschungszentrum
- Japan Agency for Medical Research and Development
- European Commission
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Université de Strasbourg
- Centre National de la Recherche Scientifique