Amiodarone induces epithelial-mesenchymal transition in A549 cells via activation of TGF-β1

Abstract

Amiodarone is a high effectiveness anti-arrhythmia agent which is able to induce pulmonary fibrosis. Many studies have shown that the epithelial-mesenchymal transition (EMT) was a significant process in pulmonary fibrosis. So far, there are no studies about whether EMT was associated with amiodarone-induced pulmonary fibrosis, which was therefore explored in this study. In addition, the underlying mechanisms of amiodarone-induced pulmonary fibrosis were examined in vitro. We found the EMT marker (α-SMA) was significantly increased, while the E-cadherin was significantly decreased in adenocarcinomic human alveolar basal epithelial cells (A549) after amiodarone treatment, suggesting that the epithelial cells were an important source of mesenchymal cells. Transforming growth factor beta1 (TGF-β1) was also increased significantly after amiodarone treatment. In conclusion, this study suggested amiodarone could induce pulmonary fibrosis via EMT, and the TGF-β1 may be a key profibrotic cytokine in mechanisms of amiodarone-induced pulmonary fibrosis.

Keywords:

• Amiodarone
• pulmonary fibrosis
• epithelial-mesenchymal transition
• A549

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by Zhejiang Provincial Natural Science Foundation of China, No. LY15H150008, LY14H180008, LQ16H040002 and LQ17H010004, Zhejiang Medicines Health Science and Technology Program, No. 2013KYA121 and 2016KYB189, WenZhou Science and Technology Bureau, No. Y20140664, Y20140688, Y20150177 and Y20160113.