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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)
Publ. Version/Full Text Research data 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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Publication type Article: Journal article
Document type Scientific Article
Keywords Progressive Pulmonary-fibrosis; Bleomycin; Activation
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 16, Issue: 1, Pages: , Article Number: 173 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) 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)
POF-Topic(s) 30202 - Environmental Health
30203 - Molecular Targets and Therapies
30201 - Metabolic Health
Research field(s) Lung Research
Environmental Sciences
Allergy
Enabling and Novel Technologies
Helmholtz Diabetes Center
PSP Element(s) G-509400-001
G-507300-001
G-552100-001
G-503300-001
G-505700-001
G-502200-001
Grants PFP - Helmholtz Postdoctoral Fellowship
European Research Council
Else-Kroner-Fresenius-Stiftung
German Research Foundation
Human Frontier Science Program Career Development Award
DOI 10.1038/s41467-024-55596-x
WOS ID 001389961400026
Scopus ID 85213941625
PubMed ID 39747171
Erfassungsdatum 2025-04-10
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