Inhibition of epithelial cell YAP-TEAD/LOX signaling attenuates pulmonary fibrosis in preclinical models

Darcy Elizabeth Wagner (), Hani N. Alsafadi, Nilay Mitash, Aurelien Justet, Qianjiang Hu, Ricardo Pineda, Claudia Staab-Weijnitz, Martina Korfei, Nika Gvazava, Kristin Wannemo, Ugochi Onwuka, Molly Mozurak, Adriana Estrada-Bernal, Juan Cala-Garcia, Katrin Mutze, Rita Costa, Deniz Bölükbas, John Stegmayr, Wioletta Skronska-Wasek, Stephan Klee, Chiharu Ota, Hoeke A. Baarsma, Jingtao Wang, John Sembrat, Anne Hilgendorff, Jun Ding, Andreas Günther, Rachel Chambers, Ivan Rosas, Stijn Langhe, Naftali Kaminski, Mareike Lehmann, Oliver Eickelberg and Melanie Königshoff ()
Additional contact information
Darcy Elizabeth Wagner: Lund University
Hani N. Alsafadi: Lund University
Nilay Mitash: Department of Medicine University of Pittsburgh
Aurelien Justet: Yale School of Medicine
Qianjiang Hu: Department of Medicine University of Pittsburgh
Ricardo Pineda: Department of Medicine University of Pittsburgh
Claudia Staab-Weijnitz: Member of the German Center for Lung Research (DZL)
Martina Korfei: Justus-Liebig-Universität Giessen
Nika Gvazava: Lund University
Kristin Wannemo: Department of Medicine University of Pittsburgh
Ugochi Onwuka: Department of Medicine University of Pittsburgh
Molly Mozurak: Department of Medicine University of Pittsburgh
Adriana Estrada-Bernal: Department of Medicine University of Pittsburgh
Juan Cala-Garcia: Department of Internal Medicine. Yale University
Katrin Mutze: Member of the German Center for Lung Research (DZL)
Rita Costa: Member of the German Center for Lung Research (DZL)
Deniz Bölükbas: Lund University
John Stegmayr: Lund University
Wioletta Skronska-Wasek: Member of the German Center for Lung Research (DZL)
Stephan Klee: Member of the German Center for Lung Research (DZL)
Chiharu Ota: Member of the German Center for Lung Research (DZL)
Hoeke A. Baarsma: Member of the German Center for Lung Research (DZL)
Jingtao Wang: Research-Institute of the McGill University Hospital
John Sembrat: Department of Medicine University of Pittsburgh
Anne Hilgendorff: Member of the German Center for Lung Research (DZL)
Jun Ding: Research-Institute of the McGill University Hospital
Andreas Günther: Justus-Liebig-Universität Giessen
Rachel Chambers: University College London
Ivan Rosas: Baylor College of Medicine
Stijn Langhe: Mayo Clinic
Naftali Kaminski: Yale School of Medicine
Mareike Lehmann: Member of the German Center for Lung Research (DZL)
Oliver Eickelberg: Department of Medicine University of Pittsburgh
Melanie Königshoff: Member of the German Center for Lung Research (DZL)

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disease characterized by excessive extracellular matrix deposition. Current IPF therapies slow disease progression but do not stop or reverse it. The (myo)fibroblasts are thought to be the main cellular contributors to excessive extracellular matrix production in IPF. Here we show that fibrotic alveolar type II cells regulate production and crosslinking of extracellular matrix via the co-transcriptional activator YAP. YAP leads to increased expression of Lysl oxidase (LOX) and subsequent LOX-mediated crosslinking by fibrotic alveolar type II cells. Pharmacological YAP inhibition via verteporfin reverses fibrotic alveolar type II cell reprogramming and LOX expression in experimental lung fibrosis in vivo and in human fibrotic tissue ex vivo. We thus identify YAP-TEAD/LOX inhibition in alveolar type II cells as a promising potential therapy for IPF patients.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-61795-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61795-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-61795-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().