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Fischer, A. ; Han, W. ; Hu, S. ; Mück-Häusl, M. ; Wannemacher, J. ; Kadri, S. ; Lin, Y. ; Dai, R. ; Christ, S. ; Su, Y. ; Dasgupta, B. ; Sardogan, A. ; Deisenhofer, C. ; Dutta, S. ; Kadri, A. ; Güney, T.G. ; Correa-Gallegos, D.* ; Mayr, C.H. ; Hatz, R.* ; Stoleriu, M.G.* ; Lindner, M.* ; Hilgendorff, A. ; Adler, H. ; Machens, H.G.* ; Schiller, H.B. ; Hauck, S.M. ; Rinkevich, Y.*

Targeting pleuro-alveolar junctions reverses lung fibrosis in mice.

Nat. Commun. 16:173 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Lung fibrosis development utilizes alveolar macrophages, with mechanisms that are incompletely understood. Here, we fate map connective tissue during mouse lung fibrosis and observe disassembly and transfer of connective tissue macromolecules from pleuro-alveolar junctions (PAJs) into deep lung tissue, to activate fibroblasts and fibrosis. Disassembly and transfer of PAJ macromolecules into deep lung tissue occurs by alveolar macrophages, activating cysteine-type proteolysis on pleural mesothelium. The PAJ niche and the disassembly cascade is active in patient lung biopsies, persists in chronic fibrosis models, and wanes down in acute fibrosis models. Pleural-specific viral therapeutic carrying the cysteine protease inhibitor Cystatin A shuts down PAJ disassembly, reverses fibrosis and regenerates chronic fibrotic lungs. Targeting PAJ disassembly by targeting the pleura may provide a unique therapeutic avenue to treat lung fibrotic diseases.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Progressive Pulmonary-fibrosis; Bleomycin; Activation
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 16, Heft: 1, Seiten: , Artikelnummer: 173 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Regenerative Biology and Medicine (IRBM)
Research Unit Precision Regenerative Medicine (PRM)
Institute of Lung Health and Immunity (LHI)
Institute of Asthma and Allergy Prevention (IAP)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Diabetes and Obesity (IDO)
Förderungen PFP - Helmholtz Postdoctoral Fellowship
European Research Council
Else-Kroner-Fresenius-Stiftung
German Research Foundation
Human Frontier Science Program Career Development Award