Transient receptor potential canonical 1 channel mediates the mechanical stress‑induced epithelial‑mesenchymal transition of human bronchial epithelial (16HBE) cells

Wang,Jing; He,Ye; Yang,Gang; Li,Na; Li,Minchao; Zhang,Min

doi:10.3892/ijmm.2020.4568

Transient receptor potential canonical 1 channel mediates the mechanical stress‑induced epithelial‑mesenchymal transition of human bronchial epithelial (16HBE) cells

Authors:
- Jing Wang
- Ye He
- Gang Yang
- Na Li
- Minchao Li
- Min Zhang
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Affiliations: Department of Respiratory Medicine, The Second Clinical Hospital of Chongqing Medical University, Chongqing 400010, P.R. China, Department of Geriatrics, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Science, Chengdu, Sichuan 610072, P.R. China, Department of Neurosurgery, The First Clinical Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Division of Nephrology, The Seventh Affiliated Hospital, Sun Yat‑sen University, Shenzhen, Guangdong 518107, P.R. China
Published online on: April 7, 2020 https://doi.org/10.3892/ijmm.2020.4568
Pages: 320-330
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Airway remodeling is a central event in the pathology of chronic obstructive pulmonary disease (COPD) that leads to airway narrowing and subsequently, to increased mechanical pressure. High mechanical pressure can exacerbate airway remodeling. Thus, a treatment regimen aimed at disrupting this high‑pressure airway remodeling vicious cycle may improve the prognosis of patients with COPD. Recent studies have demonstrated that mechanical stress induces lung epithelial‑mesenchymal transition (EMT), which is commonly present in airway epithelial cells of patients with COPD. As TRPC1 functions as a mechanosensitive channel that mediates non‑selective cation entry in response to increased membrane stretch, the present study investigated the role of TRPC1 in the occurrence of EMT induced by mechanical stress. In the present study, the expression of TRPC1 in the bronchial epithelium was examined in vivo by immunohistochemistry. In vitro, human bronchial epithelial (16HBE) cells were subjected to mechanical stretching for up to 48 h, and TRPC1 expression was then examined by RT‑qPCR and western blot analysis. In addition, TRPC1 receptor function was assessed by Ca2+ imaging and siRNA transfection. EMT was identified using immunofluorescence, western blot analysis and RT‑qPCR. It was found that TRPC1 expression was upregulated in patients with COPD and in 16HBE cells subjected to mechanical stretch. The mechanical stress‑induced activation of TRPC1 in 16HBE cells increased the intracellular calcium concentration and subsequently decreased the expression of cytokeratin 8 and E‑cadherin, and increased the expression of α‑smooth muscle actin, indicating the occurrence of EMT. On the whole, the findings of the present study demonstrate that TRPC1 plays a key role in the occurrence of EMT in human lung epithelial cells in response to mechanical stretch; thus, this protein may serve as a novel therapeutic target for progressive airway remodeling in COPD.

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