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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)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Extracellular-matrix; Taz; Differentiation; Homeostasis; Expression; Induction; Polarity; Growth
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 16, Heft: 1, Seiten: , Artikelnummer: 7099 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)
Research Unit Lung Repair and Regeneration (LRR)
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