Wagner, D.E. ; Alsafadi, H.N. ; Mitash, N.* ; Justet, A.* ; Hu, Q.* ; Pineda, R.* ; Staab-Weijnitz, C.A. ; Korfei, M.* ; Gvazava, N.* ; Wannemo, K.* ; Onwuka, U.* ; Mozurak, M.* ; Estrada-Bernal, A.* ; Cala-Garcia, J.* ; Mutze, K. ; Costa, R. ; Bölükbas, D.A.* ; Stegmayr, J.* ; Skronska-Wasek, W. ; Klee, S. ; Ota, C. ; Baarsma, H.A. ; Wang, J.* ; Sembrat, J.* ; Hilgendorff, A. ; Ding, J.* ; Günther, A.* ; Chambers, R.* ; Rosas, I.* ; de Langhe, S.* ; Kaminski, N.* ; Lehmann, M. ; Eickelberg, O.* ; Königshoff, M.
Inhibition of epithelial cell YAP-TEAD/LOX signaling attenuates pulmonary fibrosis in preclinical models.
Nat. Commun. 16:7099 (2025)
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Extracellular-matrix; Taz; Differentiation; Homeostasis; Expression; Induction; Polarity; Growth
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2025
Prepublished im Jahr
0
HGF-Berichtsjahr
2025
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 16,
Heft: 1,
Seiten: ,
Artikelnummer: 7099
Supplement: ,
Reihe
Verlag
Nature Publishing Group
Verlagsort
London
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30202 - Environmental Health
80000 - German Center for Lung Research
Forschungsfeld(er)
Lung Research
PSP-Element(e)
G-503100-001
G-501800-817
G-503100-007
G-552100-001
G-501600-005
Förderungen
Deutsche Forschungsgemeinschaft
Health Geriatric Research Education and Clinical Center (TECH-GRECC) at the VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
Lund Bioimaging Center
German Center for Lung Research (DZL)
Helmholtz Association (W2 Professorship Program)
Three Lakes Foundation (Three Lakes Consortium for Pulmonary Fibrosis)
National Institute of Health Common Funds
National Institute of Health
Chan Zuckerberg foundation
American Thoracic Society Unrestricted Grant
Breath endowment fund
Helmholtz Zentrum Muenchen Postdoctoral Fellowship
Whitaker Foundation International Scholar Award
Swedish Research Council
European Research Council (ERC)
Canada Excellence Research Chairs Program
Technology Enhancing Cognition
Copyright
Erfassungsdatum
2025-10-08