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van der Koog, L.* ; Woest, M.E.* ; Gorter, I.C.* ; Verschut, V.* ; Elferink, R.A.B.* ; Zuidhof, A.B.* ; Nugraha, D.F.* ; Koloko Ngassie, M.L.* ; Bos, S.I.T.* ; Dhakad, D. ; Wolters, J.C.* ; Horvatovich, P.L.* ; Prakash, Y.S.* ; Timens, W.* ; Yildirim, A.Ö. ; Brandsma, C.A.* ; Frijlink, H.W.* ; Nagelkerke, A.* ; Gosens, R.*

Fibroblast-derived osteoglycin promotes epithelial cell repair.

npj Reg. Med. 10:16 (2025)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
There is an urgent need for innovative therapies targeting defective epithelial repair in chronic diseases like COPD. The mesenchymal niche is a critical regulator in epithelial stem cell activation, suggesting that their secreted factors are possible potent drug targets. Utilizing a proteomics-guided drug discovery strategy, we explored the lung fibroblast secretome to uncover impactful drug targets. Our lung organoid assays identified several regenerative ligands, with osteoglycin (OGN) showing the most profound effects. Transcriptomic analyses revealed that OGN enhances alveolar progenitor differentiation, detoxifies reactive oxygen species, and strengthens fibroblast-epithelial crosstalk. OGN expression was diminished in COPD patients and smoke-exposed mice. An active fragment of OGN (leucine-rich repeat regions 4-7) replicated full-length OGN's regenerative effects, significantly ameliorating elastase-induced lung injury in lung slices and improving lung function in vivo. These findings highlight OGN as a pivotal secreted protein for alveolar epithelial repair, positioning its active fragment as a promising therapeutic for COPD.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Obstructive Pulmonary-disease; Growth-factor; Lung Repair; Regeneration; Fibrosis
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 2057-3995
e-ISSN 2057-3995
Journal npj Regenerative Medicine
Quellenangaben Volume: 10, Issue: 1, Pages: , Article Number: 16 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Lung Research
PSP Element(s) G-505000-007
Grants Netherlands X-omics Initiative (NWO)
Indonesia Endowment Fund for Education Agency (LPDP)
Indonesian Education Scholarship (BPI)Scholarship from The Agency for the Assessment and Application of Technology (BPPT) Indonesia
Stichting Astmabestrijding grant
Molecular Life and Health Program of theUniversity of Groningen
Stichting Astma Bestrijding
DOI 10.1038/s41536-025-00404-3
WOS ID 001451657200001
Scopus ID 105000997265
PubMed ID 40133363
Erfassungsdatum 2025-05-09
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