期刊论文详细信息
BMC Pulmonary Medicine
mAChRs activation induces epithelial-mesenchymal transition on lung epithelial cells
Yong-Yao Cui1  Hong-Zhuan Chen1  Zhi-Hua Yu1  Liang Zhu1  Li-Na Hou1  Wei Zhou1  Zu-Peng Xu1  Ya-Bing Tang1  Yun Song1  Kai Yang1 
[1] Department of Pharmacology, Shanghai JiaoTong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China
关键词: Signaling pathway;    Non-neuronal cholinergic system;    Lung epithelial cells;    Epithelial-mesenchymal transition (EMT);   
Others  :  866410
DOI  :  10.1186/1471-2466-14-53
 received in 2013-07-19, accepted in 2014-03-25,  发布年份 2014
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【 摘 要 】

Background

Epithelial-mesenchymal transition (EMT) has been proposed as a mechanism in the progression of airway diseases and cancer. Here, we explored the role of acetylcholine (ACh) and the pathway involved in the process of EMT, as well as the effects of mAChRs antagonist.

Methods

Human lung epithelial cells were stimulated with carbachol, an analogue of ACh, and epithelial and mesenchymal marker proteins were evaluated using western blot and immunofluorescence analyses.

Results

Decreased E-cadherin expression and increased vimentin and α-SMA expression induced by TGF-β1 in alveolar epithelial cell (A549) were significantly abrogated by the non-selective mAChR antagonist atropine and enhanced by the acetylcholinesterase inhibitor physostigmine. An EMT event also occurred in response to physostigmine alone. Furthermore, ChAT express and ACh release by A549 cells were enhanced by TGF-β1. Interestingly, ACh analogue carbachol also induced EMT in A549 cells as well as in bronchial epithelial cells (16HBE) in a time- and concentration-dependent manner, the induction of carbachol was abrogated by selective antagonist of M1 (pirenzepine) and M3 (4-DAMP) mAChRs, but not by M2 (methoctramine) antagonist. Moreover, carbachol induced TGF-β1 production from A549 cells concomitantly with the EMT process. Carbachol-induced EMT occurred through phosphorylation of Smad2/3 and ERK, which was inhibited by pirenzepine and 4-DAMP.

Conclusions

Our findings for the first time indicated that mAChR activation, perhaps via M1 and M3 mAChR, induced lung epithelial cells to undergo EMT and provided insights into novel therapeutic strategies for airway diseases in which lung remodeling occurs.

【 授权许可】

   
2014 Yang et al.; licensee BioMed Central Ltd.

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