Temporal and Spatial Expression of Transforming Growth Factor-β after Airway Remodeling to Tobacco Smoke in Rats
Autor: | Laura Hoang, Lei Wang, Yen P. Nguyen, Rayza Aspeé, Kent E. Pinkerton, Yi Hsin Shen, Suzette Smiley-Jewell, Nicholas J. Kenyon, S J Bolton |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Male Pathology Time Factors Respiratory System Clinical Biochemistry Cardiorespiratory Medicine and Haematology Cardiovascular Epithelium Transforming Growth Factor beta Metaplasia Rats Inbred SHR 2.1 Biological and endogenous factors Lymphocytes Aetiology Squamous epithelial cell Lung Cell Aggregation Original Research COPD Smoking airway epithelium transforming growth factor-β respiratory system medicine.anatomical_structure Organ Specificity Respiratory Immunohistochemistry Airway Remodeling medicine.symptom spontaneously hypertensive rats tobacco smoke Pulmonary and Respiratory Medicine medicine.medical_specialty Inbred SHR Alveolar chronic obstructive pulmonary disease Transforming Growth Factor beta1 03 medical and health sciences Transforming Growth Factor beta2 Transforming Growth Factor beta3 Internal medicine Macrophages Alveolar Tobacco medicine Animals Molecular Biology Messenger RNA Tobacco Smoke and Health business.industry Macrophages Cell Biology medicine.disease Rats respiratory tract diseases 030104 developmental biology Endocrinology Gene Expression Regulation transforming growth factor-beta Respiratory epithelium business Airway Transforming growth factor |
Zdroj: | American journal of respiratory cell and molecular biology, vol 54, iss 6 |
ISSN: | 1535-4989 |
Popis: | 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. |
Databáze: | OpenAIRE |
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