Vitronectin regulates lung tissue remodeling and emphysema in chronic obstructive pulmonary disease

Gang Liu¹, Alan C Hsu², Silke Geirnaert³, Christine Cong⁴, Prema M Nair², Sj Shen⁵, Jacqueline E Marshall⁵, Tatt Jhong Haw², Michael Fricker², Ashleigh M Philp⁶, Nicole G Hansbro⁵, Stelios Pavlidis⁷, Yike Guo⁸, Janette K Burgess⁹, Leandro Castellano¹⁰, Antonio Ieni¹¹, Gaetano Caramori¹², Brain G G Oliver¹³, K Fan Chung⁷, Ian M Adcock⁸, Darryl A Knight¹⁴, Francesca Polverino⁴, Ken Bracke³, Peter A Wark¹⁵, Philip M Hansbro¹⁶

Affiliations

¹ School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, Australia. Electronic address: gang.liu@uts.edu.au.
² Immune Health, Hunter Medical Research Institute and The University of Newcastle, Newcastle, NSW, Australia.
³ Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
⁴ Pulmonary and Critical Care Division, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
⁵ Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW, Australia.
⁶ Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW, Australia; St Vincent's Medical School, University of New South Wale Medicine, University of New South Wale, Sydney, NSW, Australia.
⁷ The Airway Disease Section, Data Science Institute, National Heart & Lung Institute, Imperial College London, London, UK.
⁸ Data Science Institute, National Heart & Lung Institute, Imperial College London, London, UK.
⁹ University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen Research Institute of Asthma and COPD, Groningen, the Netherlands.
¹⁰ School of Life Sciences, University of Sussex, Falmer, Brighton, UK.
¹¹ Department of Pathology, University of Messina, Messina, Italy.
¹² Pulmonology, Department of Medicine and Surgery, University of Parma, Parma PR, Italy.
¹³ School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, Australia.
¹⁴ Immune Health, Hunter Medical Research Institute and The University of Newcastle, Newcastle, NSW, Australia; Research and Academic Affairs, Providence Health Care Research Institute, Vancouver, BC, Canada; Departemnt of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, Faculty of Medicine, Vancouver, BC, Canada.
¹⁵ Immune Health, Hunter Medical Research Institute and The University of Newcastle, Newcastle, NSW, Australia; Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, Australia.
¹⁶ Immune Health, Hunter Medical Research Institute and The University of Newcastle, Newcastle, NSW, Australia; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW, Australia. Electronic address: philip.hansbro@uts.edu.au.

PMID: 39838644
PMCID: PMC11897773 (available on 2026-03-05)
DOI: 10.1016/j.ymthe.2025.01.032

Vitronectin regulates lung tissue remodeling and emphysema in chronic obstructive pulmonary disease

Gang Liu et al. Mol Ther. 2025.

. 2025 Mar 5;33(3):917-932.

doi: 10.1016/j.ymthe.2025.01.032. Epub 2025 Jan 21.

Authors

Affiliations

¹ School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, Australia. Electronic address: gang.liu@uts.edu.au.
² Immune Health, Hunter Medical Research Institute and The University of Newcastle, Newcastle, NSW, Australia.
³ Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
⁴ Pulmonary and Critical Care Division, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
⁵ Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW, Australia.
⁶ Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW, Australia; St Vincent's Medical School, University of New South Wale Medicine, University of New South Wale, Sydney, NSW, Australia.
⁷ The Airway Disease Section, Data Science Institute, National Heart & Lung Institute, Imperial College London, London, UK.
⁸ Data Science Institute, National Heart & Lung Institute, Imperial College London, London, UK.
⁹ University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen Research Institute of Asthma and COPD, Groningen, the Netherlands.
¹⁰ School of Life Sciences, University of Sussex, Falmer, Brighton, UK.
¹¹ Department of Pathology, University of Messina, Messina, Italy.
¹² Pulmonology, Department of Medicine and Surgery, University of Parma, Parma PR, Italy.
¹³ School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, Australia.
¹⁴ Immune Health, Hunter Medical Research Institute and The University of Newcastle, Newcastle, NSW, Australia; Research and Academic Affairs, Providence Health Care Research Institute, Vancouver, BC, Canada; Departemnt of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, Faculty of Medicine, Vancouver, BC, Canada.
¹⁵ Immune Health, Hunter Medical Research Institute and The University of Newcastle, Newcastle, NSW, Australia; Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, Australia.
¹⁶ Immune Health, Hunter Medical Research Institute and The University of Newcastle, Newcastle, NSW, Australia; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW, Australia. Electronic address: philip.hansbro@uts.edu.au.

PMID: 39838644
PMCID: PMC11897773 (available on 2026-03-05)
DOI: 10.1016/j.ymthe.2025.01.032

Abstract

Vitronectin (VTN) is an important extracellular matrix protein in tissue remodeling, but its role in chronic obstructive pulmonary disease (COPD) is unknown. We show that VTN regulates tissue remodeling through urokinase plasminogen activator (uPA) signaling pathway in COPD. In human COPD airways and bronchoepithelial cells and the airways of mice with cigarette smoke (CS)-induced experimental COPD, VTN protein was not changed, but downstream uPA signaling was altered (increased plasminogen activator inhibitor-1) that induced collagen and airway remodeling. In the parenchyma, VTN levels were decreased, uPA signaling pathway differentially altered and collagen reduced in lung fibroblasts from human and lung parenchyma in experimental COPD. Vtn inhibition with siRNA in mouse fibroblasts altered uPA signaling increased matrix metalloproteinase-12, and reduced collagen, whereas over-expression restored collagen production after CS extract challenge. Vtn^-/- and Vtn small interfering RNA-treated mice had exaggerated inflammation, emphysema, and impaired lung function compared with controls with CS-induced COPD. Restoration of VTN in the parenchyma may be a therapeutic option for emphysema and COPD.

Keywords: COPD; emphysema; remodeling; uPA pathway; vitronectin.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

References

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Vitronectin regulates lung tissue remodeling and emphysema in chronic obstructive pulmonary disease

Affiliations

Vitronectin regulates lung tissue remodeling and emphysema in chronic obstructive pulmonary disease

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous