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PMID: 16574941 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Activation of transforming growth factor-beta by the integrin alphavbeta8 delays epithelial wound closure.

American journal of respiratory cell and molecular biology ·Vol. 35 ·No. 2 ·2006-08-00 ·Pages 252-9

Neurohr C, Nishimura SL, Sheppard D

Abstract

Transforming growth factor (TGF)-beta family members regulate multiple aspects of wound repair through effects on cell proliferation, matrix production, and tissue inflammation, but the effects of TGF-beta on wound closure itself have been controversial. We found that blocking antibodies to TGF-beta enhanced the degree of closure of scratch wounds in primary airway epithelial monolayers, while addition of exogenous TGF-beta1 inhibited the degree of closure, suggesting that endogenous activation of TGF-beta normally serves as a brake on the degree of wound closure. Although these cells secreted large amounts of TGF-beta2 and small amounts of TGF-beta1, blockade of TGF-beta1 enhanced the degree of wound closure, whereas blockade of TGF-beta2 had no effect. TGF-beta1 (but not TGF-beta2) can be activated by two members of the integrin family, alphavbeta6 and alphavbeta8, which are both expressed on airway epithelial cells. Wounding induced activation of TGF-beta through effects of both integrins, but antibodies against alphavbeta8 enhanced the degree of wound closure, whereas antibodies against alphavbeta6 did not.

MeSH Terms
Antibodies, Monoclonal/pharmacology Bronchi/cytology Cell Culture Techniques Cells, Cultured Epithelial Cells/drug effects,metabolism Humans Integrins/metabolism Recombinant Proteins/metabolism Transforming Growth Factor beta/genetics,metabolism Transforming Growth Factor beta1 Transforming Growth Factor beta2 Transforming Growth Factor beta3 Wound Healing/physiology
Chemicals
Antibodies, Monoclonal Integrins Recombinant Proteins TGFB1 protein, human TGFB2 protein, human Transforming Growth Factor beta Transforming Growth Factor beta1 Transforming Growth Factor beta2 Transforming Growth Factor beta3 integrin alphavbeta8
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Neurohr Claus
Department of Medicine, Lung Biology Center, University of California, San Francisco, 94143-2922, USA.
Nishimura Stephen L
Sheppard Dean
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38 references, click to expand
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Article Info
Journal
American journal of respiratory cell and molecular biology
Abbr.
Am J Respir Cell Mol Biol
ISSN
1044-1549
DOI
10.1165/rcmb.2006-0013OC
Published
2006-08-00
Epub
2006-00-30
Pages
252-9
Language
English
Region
United States
NLM ID
8917225
PMCID
PMC2643260
Subset
IM
Grants
NHLBI NIH HHS · HL53949 · United States
NHLBI NIH HHS · HL56385 · United States
NHLBI NIH HHS · HL64353 · United States
NHLBI NIH HHS · HL66600 · United States
External Links
PubMed source DOI: 10.1165/rcmb.2006-0013OC PMC Full Text View journal details
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