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Updated: May 8, 2026

Using Nicotine in a Silica-Exposed Mouse Model to Promote Lung Epithelial-Mesenchymal Transition
Published on: March 3, 2023
Cx43 phosphorylation at Ser368 facilitates PASMC dedifferentiation in nicotine-induced pulmonary arterial remodeling
Yi Xu1, Xiaomin Hou2, Su Guo3
1School of Public Health, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi 030001, China; Environmental Exposures Vascular Disease Institute, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi 030001, China.
Background:
Pulmonary arterial hypertension is a severe disease characterized by pulmonary vascular remodeling, which is closely associated with the phenotypic switching of pulmonary artery smooth muscle cells (PASMCs). Connexin 43 (Cx43) phosphorylation is a key regulator of intercellular communication. However, the specific mechanism underlying nicotine-induced dedifferentiation of PASMCs remains unclear.
Purpose:
This study aimed to investigate the molecular mechanism by which Cx43 phosphorylation promotes nicotine-induced phenotypic switching of PASMCs, thereby driving pulmonary vascular remodeling.
Methods:
Using Tagln-Cre; Cx43+ /+ and Tagln-Cre; Cx43flox/+ deletion mice exposed to nicotine, a series of in vivo and in vitro experiments were conducted to investigate the mechanism by which nicotine promotes pulmonary arterial remodeling via protein kinase C-mediated phosphorylation of Cx43 and subsequent dedifferentiation of PASMCs. The involvement of this kinase pathway was further validated with its specific inhibitor, chelerythrine chloride.
Results:
Nicotine increased PASMC dedifferentiation by promoting Cx43 phosphorylation at Ser368 (Cx43-pS368). In Tagln-Cre; Cx43flox/+ mice, these pathological changes were reduced. In vitro, chelerythrine chloride was utilized to inhibit nicotine-induced Cx43-pS368. This suppression of Cx43-pS368 effectively attenuated nicotine-induced PASMC dedifferentiation, thereby ameliorating pulmonary arterial remodeling.
Conclusion:
Nicotine can induce PASMC phenotypic transformation by modulating Cx43-pS368, thereby promoting pulmonary artery remodeling. Targeting this pathway could provide a therapeutic strategy for nicotine-related pulmonary vascular diseases.
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