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

¹ James Hogg iCapture Center for Cardiovascular and Pulmonary Research, St. Paul's Hospital, Vancouver, British Columbia, Canada V6Z 1Y6

^* To whom correspondence should be addressed. E-mail: shayashi{at}mrl.ubc.ca.

	Abstract

Epithelial-mesenchymal transformation is now recognized as an important feature of tissue remodeling. The present report concerns the role of adenovirus infection in inducing this transformation in an animal model of COPD.

Guinea pig primary peripheral lung epithelial cells (PLE) transfected with adenovirus E1A (E1A-PLE) were compared to normal guinea pig lung fibroblasts (NLF) transfected with E1A (E1A-NLF). These cells were characterized by PCR, immunocytochemistry, electron microscopy, and Western and Northern analyses. Electrophoretic mobility shifts were performed to examine NF-B and AP-1 binding activities.

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

E1A transfection results in the transformation of PLE and NLF to a phenotype intermediate between that of the two primary cells. We postulate that this intermediate phenotype may have a major role in the remodeling of the airways in COPD associated with persistence of E1A DNA.

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