Cited by 2,076TGF-β signaling in diseasesCell Adhesion Molecules ResearchInterstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

A Mechanism for Regulating Pulmonary Inflammation and Fibrosis: The Integrin αvβ6 Binds and Activates Latent TGF β1

Open access
Munger, John S, Huang, Xiaozhu, Kawakatsu, Hisaaki, Griffiths, Mark J.D, Dalton, Stephen L, Wu, Jianfeng, Pittet, Jean-François, Kaminski, Naftali +4 more·1999·Cell

Abstract

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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Crossref · 10.1016/s0092-8674(00)80545-0

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  • Antibody-mediated inhibition of αvβ6-mediated TGF-β1 activation decreased lung fibrosis in preclinical models.

    “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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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
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
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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