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A Mechanism for Regulating Pulmonary Inflammation and Fibrosis: The Integrin αvβ6 Binds and Activates Latent TGF β1
Open accessAbstract
Transforming growth factor beta (TGF beta) family members are secreted in inactive complexes with a latency-associated peptide (LAP), a protein derived from the N-terminal region of the TGF beta gene product. Extracellular activation of these complexes is a critical but incompletely understood step in regulation of TGF beta function in vivo. We show that TGF beta 1 LAP is a ligand for the integrin alpha v beta 6 and that alpha v beta 6-expressing cells induce spatially restricted activation of TGF beta 1. This finding explains why mice lacking this integrin develop exaggerated inflammation and, as we show, are protected from pulmonary fibrosis. These data identify a novel mechanism for locally regulating TGF beta 1 function in vivo by regulating expression of the alpha v beta 6 integrin.
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“antibody-mediated inhibition of αvβ6-mediated TGF-β1 activation decreased lung fibrosis in pre-clinical models99,103”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [103]
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Metadata
- Authors
- Munger, J. S., Huang, X., Kawakatsu, H., Griffiths, M. J. D., Dalton, S. L., Wu, J., Pittet, J.-F., Kaminski, N., Garat, C., Matthay, M. A., Rifkin, D. B., & Sheppard, D.
- Affiliations
- NYU Langone Health (US)
- University of California, San Francisco (US)
- New York University (US)
- Corresponding author
- Sheppard, Dean
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1999-02
- Volume
- 96
- Issue
- 3
- Pages
- 319-328
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1998975199
- Cited by
- 2,076
- References
- 42
- Citations by year
- 2026: 59 · 2025: 59 · 2024: 77 · 2023: 66 · 2022: 83 · 2021: 74 · 2020: 79 · 2019: 69 · 2018: 76 · 2017: 93 · 2016: 84 · 2015: 79 · 2014: 91 · 2013: 82 · 2012: 91
- FWCI
- 22.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- National Institutes of Health (2r01hl047412-05a1)
- National Heart, Lung, and Blood Institute (HL 56385, HL53949, HL47412)
- NIH Clinical Center
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Keywords
- integrin αvβ6, TGF-β1, latency-associated peptide, TGF-beta activation, pulmonary fibrosis, lung inflammation, integrin-deficient mice, extracellular matrix
- MeSH terms
- Animals, Antigens, Neoplasm, Bleomycin, Epithelial Cells, Esophagus, Cricetinae, Humans, Ligands, Peptide Fragments, Protein Binding, Protein Precursors, Proteins, Pulmonary Fibrosis, Tumor Cells, Cultured, Keratinocytes, Integrins, Transforming Growth Factor beta, CHO Cells, 3T3 Cells, Mice, Knockout, Mice, Transforming Growth Factor beta1
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