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Int J Med Sci 2023; 20(10):1326-1335. doi:10.7150/ijms.86215 This issue Cite

Research Paper

Electric field promotes dermal fibroblast transdifferentiation through activation of RhoA/ROCK1 pathway

Wenping Wang^1,2#, Wanqi Huang^1#, Jie Liu^1,3#, Ze Zhang¹, Ran Ji², Chao Wu¹, Jiaping Zhang^1✉, Xupin Jiang^1✉

1. Department of Plastic Surgery, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University, Chongqing 400038, China.
2. Department of Burn and Plastic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
3. Department of Plastic and Maxillofacial Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
#These authors contributed equally to this work.

✉ Corresponding authors: Xupin Jiang, Tel: +86 023 68765973, E-mail: xpjiangedu.cn; Jiaping Zhang, Tel: +86 023 68765971, E-mail: japzhangcom.

Abstract

With the increased incidence of age-related and lifestyle-related diseases, chronic wounds are sweeping the world, where recent studies reveal that dysfunction of fibroblast plays an indispensable role. Endogenous electric field (EF) generated by skin wound disrupting an epithelial layer has been used as an alternative clinical treatment in chronic wound by modulating cellular behaviours, including fibroblasts transdifferentiation. Although many molecules and signaling pathways have been reported associated with fibroblasts transdifferentiation, studies investigating how the electric field affects the cellular pathways have been limited. For this purpose, a model of electric field treatment in vitro was established, where cells were randomly divided into control and electrified groups. The changes of protein expression and distribution were detected under different conditions, along with Zeiss imaging system observing the response of cells. Results showed that fibroblast transdifferentiation was accompanied by increased expression of a-SMA and extracellular matrix (COL-1 and COL-3) under the EF. Simultaneously, fibroblast transdifferentiation was also consistent with changes of cell arrangement and enhanced motility. Furthermore, we found that electric field activated RhoA signaling pathways activity. Y-27632, a RhoA inhibitor, which was used to treat fibroblasts, resulted in reduced transdifferentiation. The connection between electric field and RhoA signaling pathways is likely to be significant in modulating fibroblast transdifferentiation in acute injury and tissue remodeling, which provides an innovative idea for the molecular mechanism of EF in promoting chronic wound healing.

Keywords: Electric field, Myofibroblast, wound healing, chronic wound, RhoA, ROCK

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