HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Behzad, A. R. Articles by Hayashi, S. Search for Related Content PubMed PubMed Citation Articles by Behzad, A. R. Articles by Hayashi, S.

Induction of mesenchymal cell phenotypes in lung epithelial cells by adenovirus E1A

James Hogg iCapture Center for Cardiovascular and Pulmonary Research, St Paul’s Hospital, Vancouver, BC, Canada.

CORRESPONDENCE: S. Hayashi, University of British Columbia James Hogg iCapture Center for Cardiovascular and Pulmonary Research, St Paul’s Hospital, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada. Fax: 1 6048068351. E-mail: shayashi{at}mrl.ubc.ca

Keywords: Adenovirus E1A, alveolar type-II cell, epithelial–mesenchymal transformation, lung fibroblasts, pathogenesis of chronic obstructive pulmonary disease, transcription factors

Received: May 20, 2005
Accepted July 31, 2006

Epithelial–mesenchymal transformation is now recognised as an important feature of tissue remodelling. The present report concerns the role of adenovirus infection in inducing this transformation in an animal model of chronic obstructive pulmonary disease.

Guinea pig primary peripheral lung epithelial cells (PLECs) transfected with adenovirus E1A (E1A-PLECs) were compared to guinea pig normal lung fibroblasts (NLFs) transfected with E1A (E1A-NLFs). These cells were characterised by PCR, immunocytochemistry, electron microscopy, and Western and Northern blot analyses. Electrophoretic mobility shift assays were performed in order to examine nuclear factor (NF)-B and activator protein (AP)-1 binding activities.

E1A-PLECs and E1A-NLFs positive for E1A DNA, mRNA and protein expressed cytokeratin and vimentin but not smooth muscle -actin. Both exhibited cuboidal morphology and junctional complexes, but did not contain lamellar bodies or express surfactant protein A, B or C mRNAs. These two cell types differed, however, in their NF-B and AP-1 binding after lipopolysaccharide stimulation, possibly due to differences in the expression of the subunits that comprise these transcriptional complexes.

E1A transfection results in the transformation of peripheral lung epithelial cells and normal lung fibroblasts to a phenotype intermediate between that of the two primary cells. It is postulated that this intermediate phenotype may play a major role in the remodelling of the airways in chronic obstructive pulmonary disease associated with persistence of adenovirus E1A DNA.