Xu Mian, Zhang Mengsi, Wu Jingjing, Wang Jinmeng, Wu Huaze, Xu Xianting
Department of Dermatology, Wenzhou Central Hospital, Wenzhou, China.
Department of Obstetrics and Gynecology, Wenzhou Central Hospital, Wenzhou, China.
Cytojournal. 2025 Mar 12;22:32. doi: 10.25259/Cytojournal_184_2024. eCollection 2025.
Previous studies reported that esculin could protect against renal ischemia-reperfusion injury and liver injury, but its mechanism of action in skin wound healing is unclear. The Wnt/β-catenin signaling pathway plays a positive role in the wound healing process. This study aimed to investigate the effects of esculin on the rate and quality of skin wound healing in mice and explore its regulatory role in the Wnt/b-catenin signaling pathway.
Circular full-thickness skin wounds with a diameter of 8 mm were created on the backs of C57BL/6 mice, which were administered with 20 and 40 mg•kg esculin through gastric lavage. Wound healing was monitored, and samples collected on day 14 were analyzed through hematoxylin-eosin and Masson staining to assess granulation tissue formation and collagen deposition. Immunohistochemistry, immunofluorescence, and Western blot evaluated markers of collagen synthesis, proliferation, angiogenesis, and proteins in the Wnt/b-catenin signaling pathway. National institutes of health/3T3 cells treated with esculin (50 and 200 μM) were analyzed for proliferating cell nuclear antigen (PCNA) expression to assess proliferative activity.
Compared with the model group, the esculin-treated groups exhibited significantly enhanced wound healing ( < 0.05), increased skin epithelial thickness ( < 0.01), and promoted extracellular matrix formation in mice. In addition, esculin significantly raised type I collagen alpha-1 chain and type III collagen alpha-1 chain protein levels ( < 0.05), boosted the expression of the cell proliferation marker PCNA and the vascular marker cluster of differentiation 31 in the dermis ( < 0.05), and upregulated proteins related to the Wnt/b-catenin signaling pathway and increased glycogen synthase kinase 3 beta phosphorylation in skin wound and NIH/3T3 cells ( < 0.05).
Esculin could upregulate and activate the Wnt/b-catenin signaling pathway to promote wound healing.
既往研究报道七叶苷可预防肾缺血再灌注损伤和肝损伤，但其在皮肤伤口愈合中的作用机制尚不清楚。Wnt/β-连环蛋白信号通路在伤口愈合过程中起积极作用。本研究旨在探讨七叶苷对小鼠皮肤伤口愈合速度和质量的影响，并探索其在Wnt/β-连环蛋白信号通路中的调节作用。
在C57BL/6小鼠背部制造直径为8 mm的圆形全层皮肤伤口，通过灌胃给予小鼠20和40 mg•kg七叶苷。监测伤口愈合情况，并对第14天采集的样本进行苏木精-伊红染色和Masson染色分析，以评估肉芽组织形成和胶原沉积。免疫组织化学、免疫荧光和蛋白质印迹法评估胶原合成、增殖、血管生成标志物以及Wnt/β-连环蛋白信号通路中的蛋白质。对用七叶苷（50和200 μM）处理的美国国立卫生研究院/3T3细胞进行增殖细胞核抗原（PCNA）表达分析，以评估增殖活性。
与模型组相比,七叶苷处理组小鼠伤口愈合明显加快（P<0.05），皮肤上皮厚度增加（P<0.01），细胞外基质形成增加。此外，七叶苷显著提高了I型胶原α-1链和III型胶原α-1链蛋白水平（P<0.05），促进了真皮中细胞增殖标志物PCNA和血管标志物分化簇31的表达（P<0.05），上调了与Wnt/β-连环蛋白信号通路相关的蛋白质，并增加了皮肤伤口和NIH/3T3细胞中糖原合酶激酶3β的磷酸化水平（P<0.05）。
七叶苷可上调并激活Wnt/β-连环蛋白信号通路以促进伤口愈合。
