title: Temporal and Spatial Expression of Transforming Growth Factor-β after Airway Remodeling to Tobacco Smoke in Rats.
abstract: Airway remodeling is strongly correlated with the progression of chronic obstructive pulmonary disease (COPD). In this study, our goal was to characterize progressive structural changes in site-specific airways, along with the temporal and spatial expression of transforming growth factor (TGF)-β in the lungs of male spontaneously hypertensive rats exposed to tobacco smoke (TS). Our studies demonstrated that TS-induced changes of the airways is dependent on airway generation and exposure duration for proximal, midlevel, and distal airways. Stratified squamous epithelial cell metaplasia was evident in the most proximal airways after 4 and 12 weeks but with minimal levels of TGF-β-positive epithelial cells after only 4 weeks of exposure. In contrast, epithelial cells in midlevel and distal airways were strongly TGF-β positive at both 4 and 12 weeks of TS exposure. Airway smooth muscle volume increased significantly at 4 and 12 weeks in midlevel airways. Immunohistochemistry of TGF-β was also found to be significantly increased at 4 and 12 weeks in lymphoid tissues and alveolar macrophages. ELISA of whole-lung homogenate demonstrated that TGF-β2 was increased after 4 and 12 weeks of TS exposure, whereas TGF-β1 was decreased at 12 weeks of TS exposure. Airway levels of messenger RNA for TGF-β2, as well as platelet-derived growth factor-A, granulocyte-macrophage colony-stimulating factor, and vascular endothelial growth factor-α, growth factors regulated by TGF-β, were significantly decreased in animals after 12 weeks of TS exposure. Our data indicate that TS increases TGF-β in epithelial and inflammatory cells in connection with airway remodeling, although the specific role of each TGF-β isoform remains to be defined in TS-induced airway injury and disease.
authors.affiliation: 1 Center for Health and the Environment, University of California, Davis, California.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Hoang
authors.affiliation: 1 Center for Health and the Environment, University of California, Davis, California.
authors.forename: Yen P
authors.initials: YP
authors.lastname: Nguyen
authors.affiliation: 1 Center for Health and the Environment, University of California, Davis, California.
authors.forename: Rayza
authors.initials: R
authors.lastname: Aspeé
authors.affiliation: 2 Respiratory, Inflammation and Autoimmunity Innovative Medicine and Early Development Unit AstraZeneca R&D Mölndal, Mölndal, Sweden; and.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Bolton
authors.affiliation: 1 Center for Health and the Environment, University of California, Davis, California.
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Shen
authors.affiliation: 1 Center for Health and the Environment, University of California, Davis, California.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: 3 Department of Pulmonary and Critical Care Medicine, School of Medicine, University of California, Davis, California.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Kenyon
authors.affiliation: 1 Center for Health and the Environment, University of California, Davis, California.
authors.forename: Suzette
authors.initials: S
authors.lastname: Smiley-Jewell
authors.affiliation: 1 Center for Health and the Environment, University of California, Davis, California.
authors.forename: Kent E
authors.identifier: 0000-0001-9047-0353
authors.initials: KE
authors.lastname: Pinkerton
mesh_terms: D056151:Airway Remodeling / Q000235:genetics*; D000818:Animals; D002449:Cell Aggregation; D004848:Epithelium / Q000473:pathology; D005786:Gene Expression Regulation; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D009928:Organ Specificity / Q000235:genetics; D011918:Rats, Inbred SHR; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3
keywords: airway epithelium; chronic obstructive pulmonary disease; spontaneously hypertensive rats; tobacco smoke; transforming growth factor-β