TGFβ-induced epithelial to mesenchymal transition (EMT) as a model of COPD

Abstract

Epithelial to mesenchymal transition (EMT) is implicated as a core pathogenesis of chronic obstructive pulmonary disease (COPD) and may provide the link between smoking, airway fibrosis/destruction and lung cancer. Transforming growth factor beta (TGFβ) is a known inducer of EMT and the TGFβ pathway is up-regulated in the bronchial epithelium of smokers and COPD patients. Here we assess whether TGFβ-induced EMT is a useful model of early stage COPD. TGFβ treatment of the transformed cell line BEAS-2B induced the classic EMT phenotype of reduction in E-cadherin with up-regulation of N-cadherin and vimentin. However S100A4, up-regulation of which is a hallmark in vivo of active airway EMT in smokers and COPD patients, was down-regulated following TGFβ treatment. In primary human bronchial epithelial cells (pHBECs) from non-smokers, TGFβ treatment caused an increase in N-cadherin and vimentin expression but no change on E-cadherin and paradoxically a decrease in S100A4. BEAS-2B cells express relatively high levels of TGFβ constitutively while pHBECs from non-smokers, smokers and COPD patients produce TGFβ at barely detectable levels. BEAS-2B cells are more mesenchymal than pHBECs from non-smokers and treatment with a TGFβ inhibitor returns them to a more epithelial state. In conclusion, TGFβ can induce a partial EMT-like picture in bronchial epithelial cells but is not sufficient to fully replicate the in vivo phenotype. Also, BEAS-2B cells have a partial EMT phenotype at baseline and therefore may not be a suitable substitute for primary cells for EMT studies. Although the TGFβ pathway is activated in COPD, TGFβ does not seem to be the full explanation for what is driving the process.