help button home button Am J Pathol R & D Systems
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Araya, J.
Right arrow Articles by Nishimura, S. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Araya, J.
Right arrow Articles by Nishimura, S. L.
(American Journal of Pathology. 2006;169:405-415.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.060049

Integrin-Mediated Transforming Growth Factor-ß Activation Regulates Homeostasis of the Pulmonary Epithelial-Mesenchymal Trophic Unit

Jun Araya, Stephanie Cambier, Alanna Morris, Walter Finkbeiner and Stephen L. Nishimura

From the Department of Pathology, University of California–San Francisco, San Francisco, California

Trophic interactions between pulmonary epithelial and mesenchymal cell types, known as the epithelial-mesenchymal trophic unit (EMTU), are crucial in lung development and lung disease. Transforming growth factor (TGF)-ß is a key factor in mediating these interactions, but it is expressed in a latent form that requires activation to be functional. Using intact fetal tracheal tissue and primary cultures of fetal tracheal epithelial cells and fibroblasts, we demonstrate that a subset of integrins, {alpha}vß6 and {alpha}vß8, are responsible for almost all of the TGF-ß activation in the EMTU. Both {alpha}vß8 and {alpha}vß6 contribute to fetal tracheal epithelial activation of TGF-ß, whereas only {alpha}vß8 contributes to fetal tracheal fibroblast activation of TGF-ß. Interestingly, fetal tracheal epithelial {alpha}vß8-mediated TGF-ß activation can be enhanced by phorbol esters, likely because of the increased activity of MT1-MMP, an essential co-factor in {alpha}vß8-mediated activation of TGF-ß. Autocrine {alpha}vß8-mediated TGF-ß activation by fetal tracheal fibroblasts results in suppression of both transcription and secretion of hepatocyte growth factor, which is sufficient to affect phosphorylation of the airway epithelial hepatocyte growth factor receptor, c-Met, as well as airway epithelial proliferation in a co-culture model of the EMTU. These findings elucidate the function and complex regulation of integrin-mediated activation of TGF-ß within the EMTU.




This article has been cited by other articles:


Home page
 J. Cell Biol.Home page
P.-J. Wipff, D. B. Rifkin, J.-J. Meister, and B. Hinz
Myofibroblast contraction activates latent TGF- 1 from the extracellular matrix
J. Cell Biol., December 17, 2007; 179(6): 1311 - 1323.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
F. Chen, T. J. Desai, J. Qian, K. Niederreither, J. Lu, and W. V. Cardoso
Inhibition of Tgf{beta} signaling by endogenous retinoic acid is essential for primary lung bud induction
Development, August 15, 2007; 134(16): 2969 - 2979.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Biol.Home page
Z. Yang, Z. Mu, B. Dabovic, V. Jurukovski, D. Yu, J. Sung, X. Xiong, and J. S. Munger
Absence of integrin-mediated TGF{beta}1 activation in vivo recapitulates the phenotype of TGF{beta}1-null mice
J. Cell Biol., March 12, 2007; 176(6): 787 - 793.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the American Society for Investigative Pathology.