Versican expression from lung fibroblasts suppresses pulmonary fibrosis
The activation and accumulation of lung fibroblasts, leading to excessive ECM deposition, is a pathogenic hallmark of Idiopathic Pulmonary Fibrosis, a lethal and currently untreatable disease. In this report, increased expression of Versican, a multifunctional ECM proteoglycan, is detected in both human and mouse pulmonary fibrosis, mainly in monocytic cells and fibroblasts. Ubiquitous genetic reduction of Versican expression in mice promotes collagen expression and polymerisation, alters pulmonary ECM composition and structure, and exacerbates pulmonary fibrosis, delaying its resolution. Moreover, the decrease in Versican in the ECM and the ensuing reorganisation stimulate Tenascin-C expression from fibroblasts, which is further shown to be a potent Toll-like receptor 4-dependent podosome inducer, promoting ECM invasion. Thus, fibroblast-expressed Versican regulates the underlying ECM composition and structure and suppresses autologous podosome formation, limiting ECM invasion and pulmonary fibrosis.
Authors
- Sofia Grammenoudi (ORCID: https://orcid.org/0009-0002-2273-5860)
- Dionysiοs Fanidis (ORCID: https://orcid.org/0000-0002-4053-2090)
- Nuria Getino Gavara
- África Martínez Blanco
- Vagelis Rinotas (ORCID: https://orcid.org/0000-0002-2390-3136)
- Apostolos Galaris
- Paraskevi Kanellopoulou
- Ilianna Barbayianni
- Ioanna Tremi (ORCID: https://orcid.org/0000-0002-4711-8888)
- Sophia Havaki (ORCID: https://orcid.org/0000-0003-0660-2179)
- Dimitris Nastos
- Martina Samiotaki (ORCID: https://orcid.org/0000-0001-9952-0636)
- Ioannis Vamvakaris (ORCID: https://orcid.org/0000-0002-2917-7155)
- Ioannis P. Tomos (ORCID: https://orcid.org/0000-0002-9978-4823)
- Maria Shira
- Hideto Watanabe
- Vassilis Aidinis
- Christiana Magkrioti
- Eleni Katsiouli
- Stefanos Smyrniotis
Institutions
- Aichi Medical University (JP)
- University of Dundee (GB)
- National and Kapodistrian University of Athens (GR)
- Academy of Athens (GR)
- Manchester Academic Health Science Centre (GB)
- Ninewells Hospital (GB)
- University of Surrey (GB)
- University of Manchester (GB)
- Institute for Molecular Science (JP)
- Sotiria General Hospital (GR)
- Alexander Fleming Biomedical Sciences Research Center (GR)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-01-21
- DOI
- https://doi.org/10.1038/s41467-026-68377-5
- Primary Topic
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Hellenic Foundation for Research and Innovation