Ge, Q and Krimmer, D and Chen, L and Burgess, J and Black, J and Oliver, BG, Cigarette smoke induces a distinct fibrotic signature in bronchial epithelial cells in comparison to TGFß, American Journal of Respiratory and Critical Care Medicine, May 18-23, 2012, San Francisco, California, pp. 4584. ISSN 0903-1936 (2012) [Conference Extract]
|PDF (2012 Am J Respir Crit Care Med 185;2012:A2021)|
Rationale: We have previously shown cigarette smoke extract (CSE) induces the production of the extracellular matrix proteins fibronectin and perlecan in human lung fibroblasts (Krimmer et al AJRCMB 2011). The proteins were also induced by transforming growth factor β (TGFβ); however the signal transduction pathways activated by CSE were different to those used by TGFβ. These differences lead us to speculate that if we were to look at an increased number of molecules involved in the development of fibrosis, we would find differential upregulation by TGFβ and CSE.
Aim: To compare fibrosis related genes upregulated by TGFβ or CSE in primary human bronchial epithelial (HBE) cells.
Methods: HBE cells were grown to confluence in BEGM in the absence or presence of 5ng/ml of TGFβ1 or 5% CSE. Total RNA were collected after 72 hours. The expression of fibrosis related genes was measured by real time PCR. In total we examined 85 fibrosis related genes. A cut off of a minimum of 1.5 fold induction was used to indicate upregulation of a gene.
Results: TGFβ upregulated 49 different fibrosis associated genes, CSE upregulated only 16, and of all the upregulated genes, 4 were uniquely upregulated by CSE (catenin β1, extracellular matrix protein 1, and TIMP 1 and 2). As expected, TGFβ upregulated a variety of ECM proteins (eg collagen I, IV-VIII, fibronectin); integrins (eg integrin α2, α4-6), and degradative enzymes (eg matrix metalloproteinase (MMP) 1-3, 9-16). In contrast, CSE upregulated only two collagens (XI and XIV) and MMP9.
Conclusion: As CSE selectively upregulated a subset of TGF-β induced genes, elucidation of the specific mechanisms involved is likely to give novel insight into the pathophysiology of COPD.
|Item Type:||Conference Extract|
|Keywords:||Cigarette smoke extract; Bronchial Epithelial Cells; Chronic Obstructive Pulmonary Disease|
|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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