Department of Plastic Surgery, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University, Chongqing 400038, China.
Department of Burn and Plastic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Int J Med Sci. 2023 Aug 28;20(10):1326-1335. doi: 10.7150/ijms.86215. eCollection 2023.
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 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.
随着与年龄相关和与生活方式相关疾病的发病率增加，慢性伤口正在席卷全球，最近的研究表明，成纤维细胞功能障碍在其中起着不可或缺的作用。皮肤伤口产生的内源性电场 (EF) 破坏上皮层，已被用作慢性伤口的替代临床治疗方法，可调节包括成纤维细胞转分化在内的细胞行为。尽管已经报道了许多与成纤维细胞转分化相关的分子和信号通路，但研究电场如何影响细胞通路的研究还很有限。为此，建立了电场治疗模型，其中细胞随机分为对照组和通电组。在不同条件下检测蛋白表达和分布的变化，并使用蔡司成像系统观察细胞的反应。结果表明，在 EF 下，成纤维细胞转分化伴随着 a-SMA 和细胞外基质 (COL-1 和 COL-3) 的表达增加。同时，成纤维细胞转分化也与细胞排列的变化和运动性增强一致。此外，我们发现电场激活了 RhoA 信号通路的活性。RhoA 抑制剂 Y-27632 用于治疗成纤维细胞，导致转分化减少。电场与 RhoA 信号通路之间的联系可能在调节急性损伤和组织重塑中的成纤维细胞转分化中具有重要意义，这为 EF 促进慢性伤口愈合的分子机制提供了新的思路。
