Chen, L and Ge, Q and Faiz, A and Black, JL and Burgess, JK and Oliver, BG, Cigarette Smoke Extract And Tgf-β1 Induce Distinctive Expression Of Extracellular Matrix And Adhesion Molecule Genes In COPD And Non-COPD Airway Smooth Muscle Cells, American Journal of Respiratory and Critical Care Medicine, May 17-22, 2013, Philadelphia Pennsylvania ISSN 1073-449X (2013) [Conference Extract]
|PDF (2013 Am J Respir Crit Care Med 187;2013:A2015)|
Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by thickened and narrowed small bronchioles and destruction of the alveolar gas exchange surfaces. The increased thickness of the airway wall in COPD is closely related to the abnormal and exaggerated deposition of extracellular matrix (ECM) proteins. The pathological cause of this induction is not known, although it is likely that cigarette smoke and transforming growth factor beta 1 (TGF-β ) are involved. The aim of this study was to compare the ECM and 1 adhesion molecule related gene expression in COPD and non COPD primary airway smooth muscle (ASM) cells stimulated by cigarette smoke extract (CSE) or TGF-β.
Methods: Primary human ASM cells obtained from smoking donors with (n=3) and without COPD (n=3) were stimulated in vitro with 5% CSE or 10ng/ml TGF-β . Total RNA lysates were collected after 48 hours and pooled. A total of 84 ECM and adhesion molecule related 1 genes were examined by using a real time PCR array. Data were normalized to 18S rRNA and expressed as fold change compared with the unstimulated control. A cut off of 2 fold was used to indicate up-regulation.
Results: In total, 70 of the ECM and adhesion molecule associated genes can be detected in basal conditions. TGF-β up-regulated 27 of 1 the 70 genes in COPD ASM cells and 28 of the 70 genes in non COPD ASM cells, with 26 of the genes being up-regulated in both cell types. CSE however up-regulated 44 of the 70 genes in COPD ASM cells and 36 of the 70 genes in non COPD ASM cells, and 32 of these genes were up-regulated in both groups. Among the genes up-regulated by CSE, 5 genes (collagen type I, V, VIII, XV, and thrombospondin 2) were at least 1.5 times higher in COPD ASM cells than non COPD ASM cells. In contrast, 6 genes (matrix metalloproteinases 1, 12, 14, ADAM metalloproteinases with thrombospondin type 1 motif, 8, and selectin L) were at least 1.5 times lower in COPD ASM cells than non COPD ASM cells.
Conclusions: Overall CSE up-regulated more ECM and adhesion molecule associated genes than TGF-β . After stimulation with CSE collagen genes were up-regulated to a greater extent in COPD versus non-COPD ASM cells, however, matrix metalloproteinase genes had impaired up-regulation in COPD cells.
|Item Type:||Conference Extract|
|Keywords:||Airway smooth muscle; Chronic Obstructive Pulmonary Disease; Cigarette Smoke Extract; TGF-beta 1|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Cardiovascular medicine and haematology|
|Research Field:||Respiratory diseases|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Chen, L (Dr Ling Chen)|
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