Latent adenoviral infection induces production of growth factors relevant to airway remodeling in COPD.
Previous studies showed an association between latent adenoviral infection with expression of the adenoviral E1A gene and chronic obstructive pulmonary disease (COPD). The present study focuses on how the adenoviral E1A gene could alter expression of growth factors by human bronchial epithelial (HBE) cells. The data show that connective tissue growth factor (CTGF) and transforming growth factor (TGF)-beta 1 mRNA and protein expression were upregulated in E1A-positive HBE cells. Upregulation of CTGF in this in vitro model was independent of TGF-beta secreted into the growth medium. Comparison of E1A-positive with E1A-negative HBE cells showed that both expressed cytokeratin but only E1A-positive cells expressed the mesenchymal markers vimentin and alpha-smooth muscle actin. We conclude that latent infection of epithelial cells by adenovirus E1A could contribute to airway remodeling in COPD by the viral E1A gene, inducing TGF-beta 1 and CTGF expression and shifting cells to a more mesenchymal phenotype.
D017500:Adenovirus E1A Proteins / Q000235:genetics; D017501:Adenovirus E1B Proteins / Q000235:genetics; D000258:Adenovirus Infections, Human / Q000150:complications* / Q000503:physiopathology*; D001980:Bronchi / Q000166:cytology; D002454:Cell Differentiation; D055513:Connective Tissue Growth Factor; D003470:Culture Media; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology / Q000821:virology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology* / Q000821:virology*; D012333:RNA, Messenger / Q000032:analysis; D020545:Respiratory Mucosa / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; C526317:CCN2 protein, human; D003470:Culture Media; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor