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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-7-23
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pubmed:abstractText |
Transforming growth factor (TGF)-beta is a potent multifunctional cytokine that is an essential regulator of epithelial proliferation. Because TGF-beta is expressed almost entirely in a latent state in vivo, a major source of regulation of TGF-beta function is its activation. A subset of integrins, alphavbeta8 and alphavbeta6, which are expressed in the human airway, has recently been shown to activate latent TGF-beta in vitro, suggesting a regulatory role for integrins in TGF-beta function in vivo. Here we have developed a novel, biologically relevant experimental model of human airway epithelium using intact human bronchial tissue. We have used this model to determine the function of integrin-mediated activation of TGF-beta in the airway. In human bronchial fragments cultured in vitro, authentic epithelial-stromal interactions were maintained and integrin and TGF-beta expression profiles correlated with profiles found in normal lung. In addition, in this model, we found that either the integrin alphavbeta8 or TGF-beta could inhibit airway epithelial cell proliferation. Furthermore, we found that one mechanism of integrin-alphavbeta8-dependent inhibition of cell proliferation was through activation of TGF-beta because anti-beta8 antibody blocked the majority (76%) of active TGF-beta released from bronchial fragments. These data provide compelling evidence for a functional role for integrin-mediated activation of TGF-beta in control of human airway epithelial proliferation in vivo.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-10025398,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-10190283,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-10421830,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-10446041,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-10620816,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-10652271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-10793168,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-10849473,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-11156415,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-11544191,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-11586292,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-11683383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-11970960,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-12145193,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-12237923,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-12415008,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-1540382,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-1918072,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-7517145,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-7525578,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-7673344,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-8179182,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-8703475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-8918373,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-9170210,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-9252563,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-9434631,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-9593935,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-9620938,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-9657149,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-9659584,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-9662371,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-9725916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12875973-9730861
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0002-9440
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
163
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
533-42
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:12875973-Aged,
pubmed-meshheading:12875973-Aged, 80 and over,
pubmed-meshheading:12875973-Bronchi,
pubmed-meshheading:12875973-Cell Division,
pubmed-meshheading:12875973-Culture Techniques,
pubmed-meshheading:12875973-Female,
pubmed-meshheading:12875973-Gene Expression Profiling,
pubmed-meshheading:12875973-Homeostasis,
pubmed-meshheading:12875973-Humans,
pubmed-meshheading:12875973-Integrins,
pubmed-meshheading:12875973-Keratins,
pubmed-meshheading:12875973-Ki-67 Antigen,
pubmed-meshheading:12875973-Male,
pubmed-meshheading:12875973-Middle Aged,
pubmed-meshheading:12875973-Respiratory Mucosa,
pubmed-meshheading:12875973-Transforming Growth Factor beta
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pubmed:year |
2003
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pubmed:articleTitle |
Integrin alphavbeta8-mediated activation of transforming growth factor-beta inhibits human airway epithelial proliferation in intact bronchial tissue.
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pubmed:affiliation |
Department of Anatomic Pathology and Lung Biology Center, San Francisco General Hospital, University of California at San Francisco/Mt. Zion Cancer Center, San Francisco, California 94110, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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