Decreased Laminin Expression by Human Lung Epithelial Cells and Fibroblasts Cultured in Acellular Lung Scaffolds from Aged Mice
Open accessAbstract
The lung changes functionally and structurally with aging. However, age-related effects on the extracellular matrix (ECM) and corresponding effects on lung cell behavior are not well understood. We hypothesized that ECM from aged animals would induce aging-related phenotypic changes in healthy inoculated cells. Decellularized whole organ scaffolds provide a powerful model for examining how ECM cues affect cell phenotype. The effects of age on ECM composition in both native and decellularized mouse lungs were assessed as was the effect of young vs old acellular ECM on human bronchial epithelial cells (hBECs) and lung fibroblasts (hLFs). Native aged (1 year) lungs demonstrated decreased expression of laminins α3 and α4, elastin and fibronectin, and elevated collagen, compared to young (3 week) lungs. Proteomic analyses of decellularized ECM demonstrated similar findings, and decellularized aged lung ECM contained less diversity in structural proteins compared to young ECM. When seeded in old ECM, hBECs and hLFs demonstrated lower gene expression of laminins α3 and α4, respectively, as compared to young ECM, paralleling the laminin deficiency of aged ECM. ECM changes appear to be important factors in potentiating aging-related phenotypes and may provide clues to mechanisms that allow for aging-related lung diseases.
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ECM from aged lung contains less structural protein diversity.
“Research using acellularized lungs, where all cells have been removed and only the ECM remains, has illustrated that ECM from aged lung contains less structural protein diversity (93).”
From Aging and Lung Disease (2020) · cites this paper as [93]
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References 55 · Cited by 68
- Authors
- Godin, L. M., Sandri, B. J., Wagner, D. E., Meyer, C. M., Price, A. P., Akinnola, I., Weiss, D. J., & Panoskaltsis-Mortari, A.
- Affiliations
- University of Minnesota (US)
- University of Vermont (US)
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-03-08
- Volume
- 11
- Issue
- 3
- Pages
- e0150966
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4783067
- OpenAlex
- W2293634919
- Cited by
- 68
- References
- 55
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 10 · 2020: 7 · 2019: 7 · 2018: 4 · 2017: 8 · 2016: 5
- FWCI
- 8.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- National Science Foundation (1147079, P20GM103449)
- University of Minnesota (T32 GM008244)
- University of Vermont
- National Institutes of Health (1147079, NIH T32, HL07741, GM008244)
- National Heart, Lung, and Blood Institute (HL07741, R01HL108627, T32HL076122, RC4HL106625, R21HL108689, T32HL007741, R01HL107612, R21HL102570, HL076122)
- National Institute of General Medical Sciences (T32GM008244, T32GM113846, P20GM103449)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Keywords
- lung aging, extracellular matrix, decellularized lung scaffolds, laminin alpha 3, laminin α4, human bronchial epithelial cells, lung fibroblasts, elastin, fibronectin, collagen
- MeSH terms
- Age Factors, Animals, Extracellular Matrix, Female, Fibroblasts, Laminin, Lung, Male, Phenotype, Thromboplastin, Cadherins, Gene Expression, Extracellular Matrix Proteins, Cell Culture Techniques, Gene Expression Profiling, Mice, Alveolar Epithelial Cells
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