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Theranostics 2020; 10(19):8528-8540. doi:10.7150/thno.46002 This issue Cite

Research Paper

Increased intracellular Cl- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway

Wenjie Huang1,3*, Meiling Tan1*, Yue Wang2,4, Lei Liu2, Yan Pan2, Jingjing Li2, Mingxing Ouyang2, Chunjiao Long1, Xiangping Qu1, Huijun Liu1, Chi Liu1, Jia Wang1, Linhong Deng2✉, Yang Xiang1✉, Xiaoqun Qin1✉

1. School of Basic Medicine, Central South University, Changsha, Hunan 410078, China.
2. Changzhou Key Laboratory of Respiratory Medical Engineering, Institute of Biomedical Engineering and Health Sciences, Changzhou, Jiangsu 213164, China.
3. Affiliated Liutie Central Hospital of Guangxi medical university, Liuzhou, Guangxi 545007, China.
4. School of Nursing, Changzhou University, Changzhou, Jiangsu 213164, China.
*These authors contributed equally to this work.

✉ Corresponding authors: Dr. Yang Xiang (xiangyangedu.cn); Dr. Xiaoqun Qin (qinxiaoqunedu.cn); Dr. Linhong, Deng (dlhedu.cn).

Citation:
Huang W, Tan M, Wang Y, Liu L, Pan Y, Li J, Ouyang M, Long C, Qu X, Liu H, Liu C, Wang J, Deng L, Xiang Y, Qin X. Increased intracellular Cl- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway. Theranostics 2020; 10(19):8528-8540. doi:10.7150/thno.46002. https://www.thno.org/v10p8528.htm
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Abstract

Graphic abstract

In the airway, Cl- is the most abundant anion and is critically involved in transepithelial transport. The correlation of the abnormal expression and activation of chloride channels (CLCs), such as cystic fibrosis transmembrane conductance regulators (CFTRs), anoctamin-1, and CLC-2, with cell migration capability suggests a relationship between defective Cl- transport and epithelial wound repair. However, whether a correlation exists between intracellular Cl- and airway wound repair capability has not been explored thus far, and the underlying mechanisms involved in this relationship are not fully defined.

Methods: In this work, the alteration of intracellular chloride concentration ([Cl-]i) was measured by using a chloride-sensitive fluorescent probe (N-[ethoxycarbonylmethyl]-6-methoxyquinolium bromide).

Results: We found that clamping with high [Cl-]i and 1 h of treatment with the CLC inhibitor CFTR blocker CFTRinh-172 and chloride intracellular channel inhibitor IAA94 increased intracellular Cl- concentration ([Cl-]i) in airway epithelial cells. This effect improved epithelial cell migration. In addition, increased [Cl-]i in cells promoted F-actin reorganization, decreased cell stiffness, and improved RhoA activation and LIMK1/2 phosphorylation. Treatment with the ROCK inhibitor of Y-27632 and ROCK1 siRNA significantly attenuated the effects of increased [Cl-]i on LIMK1/2 activation and cell migration. In addition, intracellular Ca2+ concentration was unaffected by [Cl-]i clamping buffers and CFTRinh-172 and IAA94.

Conclusion: Taken together, these results suggested that Cl- accumulation in airway epithelial cells could activate the RhoA/ROCK/LIMK cascade to induce F-actin reorganization, down-regulate cell stiffness, and improve epithelial migration.

Keywords: Airway epithelial cells, Intracellular chloride, MQAE, Epithelial migration, Cell stiffness

Citation styles

APA
Huang, W., Tan, M., Wang, Y., Liu, L., Pan, Y., Li, J., Ouyang, M., Long, C., Qu, X., Liu, H., Liu, C., Wang, J., Deng, L., Xiang, Y., Qin, X. (2020). Increased intracellular Cl- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway. Theranostics, 10(19), 8528-8540. https://doi.org/10.7150/thno.46002.

ACS
Huang, W.; Tan, M.; Wang, Y.; Liu, L.; Pan, Y.; Li, J.; Ouyang, M.; Long, C.; Qu, X.; Liu, H.; Liu, C.; Wang, J.; Deng, L.; Xiang, Y.; Qin, X. Increased intracellular Cl- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway. Theranostics 2020, 10 (19), 8528-8540. DOI: 10.7150/thno.46002.

NLM
Huang W, Tan M, Wang Y, Liu L, Pan Y, Li J, Ouyang M, Long C, Qu X, Liu H, Liu C, Wang J, Deng L, Xiang Y, Qin X. Increased intracellular Cl- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway. Theranostics 2020; 10(19):8528-8540. doi:10.7150/thno.46002. https://www.thno.org/v10p8528.htm

CSE
Huang W, Tan M, Wang Y, Liu L, Pan Y, Li J, Ouyang M, Long C, Qu X, Liu H, Liu C, Wang J, Deng L, Xiang Y, Qin X. 2020. Increased intracellular Cl- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway. Theranostics. 10(19):8528-8540.

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