Targeting acid ceramidase inhibits YAP/TAZ signaling to reduce fibrosis in mice

Author:

Alsamman Sarah1ORCID,Christenson Stephanie A.2ORCID,Yu Amy1,Ayad Nadia M. E.34ORCID,Mooring Meghan S.5ORCID,Segal Joe M.1,Hu Jimmy Kuang-Hsien6ORCID,Schaub Johanna R.7,Ho Steve S.7,Rao Vikram7ORCID,Marlow Megan M.7,Turner Scott M.7,Sedki Mai8ORCID,Pantano Lorena9ORCID,Ghoshal Sarani10,Ferreira Diego Dos Santos11ORCID,Ma Hsiao-Yen12,Duwaerts Caroline C.113ORCID,Espanol-Suner Regina14,Wei Lan10ORCID,Newcomb Benjamin15ORCID,Mileva Izolda15,Canals Daniel15ORCID,Hannun Yusuf A.15ORCID,Chung Raymond T.16ORCID,Mattis Aras N.1317ORCID,Fuchs Bryan C.10ORCID,Tager Andrew M.18,Yimlamai Dean5ORCID,Weaver Valerie M.34141920ORCID,Mullen Alan C.16ORCID,Sheppard Dean212ORCID,Chen Jennifer Y.113ORCID

Affiliation:

1. Department of Medicine, University of California, San Francisco, San Francisco, CA 94115, USA.

2. Division of Pulmonary, Critical Care, Allergy and Sleep, Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.

3. Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.

4. UC Berkeley–UCSF Graduate Program in Bioengineering, San Francisco, CA 94143, USA.

5. Division of Pediatric Gastroenterology and Hepatology, Yale University School of Medicine, New Haven, CT 06520, USA.

6. Division of Oral Biology & Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.

7. Pliant Therapeutics, South San Francisco, CA 94080, USA.

8. Internal Medicine, Kaiser Permanente, San Francisco, CA 94115, USA.

9. Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.

10. Division of Surgical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.

11. Athinoula A. Martinos Center for Biomedical Imaging, Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

12. Lung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.

13. Liver Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.

14. Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.

15. Departments of Medicine and Biochemistry and Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA.

16. Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.

17. Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.

18. Division of Pulmonary and Critical Care Medicine, Fibrosis Research Center, and Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.

19. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.

20. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.

Abstract

Acid ceramidase inhibition promotes YAP/TAZ degradation to inactivate fibroblasts, decrease matrix stiffness, and reduce fibrosis in mice.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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