Fan Yan, Guo Xuesong, Tian Yu, Li Jie, Xi Hongwei
Department of Paediatrics, Shanxi Medical University, Shanxi, China; Department of Burns and Plastic Surgery, Children's Hospital of Shanxi (Women Health Center of Shanxi), Shanxi, China.
Department of Burns and Plastic Surgery, Children's Hospital of Shanxi (Women Health Center of Shanxi), Shanxi, China.
Biomol Biomed. 2024 Dec 11;25(1):249-258. doi: 10.17305/bb.2024.10906.
Hypertrophic scar (HS) is a fibrous proliferative disorder that occurs in the dermis after skin injury. Studies have confirmed that Botulinum toxin type A (BTA) is effective in scar prevention and treatment. However, the specific mechanism remains uncertain. Hypertrophic scar fibroblasts (HSFs) and normal skin fibroblasts (NSFs) from the skin tissues of HS patients were isolated and cultured. Western blot analysis was conducted to measure the expression of JAK2/STAT3 pathway-related proteins. HSFs were treated with the JAK2 inhibitor (AG490) or agonist (C-A1). The CCK-8 assay, EdU staining, scratch-wound assay and transwell assay were used to examine the biological properties of HSFs. Western blot, immunofluorescence, and Sirius red staining were used to assess the fibrosis of HSFs. Additionally, a mouse full-thickness wound model was constructed to investigate the role of BTA in wound healing. The results showed that the JAK2 and STAT3 phosphorylation levels were markedly increased in HS tissues and HSFs. AG490 treatment reduced cell viability, proliferation and migration capacity, and inhibited the fibrosis of HSFs, whereas C-A1 treatment had the opposite effect. BTA treatment inhibited the JAK2/STAT3 pathway. BTA reduced cell viability, proliferation and migration ability, and inhibited the fibrosis of HSFs, while C-A1 intervention weakened the impact of BTA. Meanwhile, BTA promoted wound healing and reduced collagen deposition in vivo. In conclusion, BTA inhibited the JAK2/STAT3 pathway, which in turn hindered the proliferation, migration and fibrosis of HSFs, and promoted wound healing in mice.
增生性瘢痕（HS）是一种在皮肤损伤后发生于真皮层的纤维增生性疾病。研究证实，A型肉毒杆菌毒素（BTA）在瘢痕预防和治疗中有效。然而，具体机制仍不确定。从增生性瘢痕患者的皮肤组织中分离并培养增生性瘢痕成纤维细胞（HSFs）和正常皮肤成纤维细胞（NSFs）。进行蛋白质免疫印迹分析以检测JAK2/STAT3信号通路相关蛋白的表达。用JAK2抑制剂（AG490）或激动剂（C-A1）处理HSFs。采用CCK-8检测、EdU染色、划痕实验和Transwell实验检测HSFs的生物学特性。通过蛋白质免疫印迹、免疫荧光和天狼星红染色评估HSFs的纤维化情况。此外，构建小鼠全层皮肤缺损模型以研究BTA在伤口愈合中的作用。结果显示，增生性瘢痕组织和HSFs中JAK2和STAT3的磷酸化水平显著升高。AG490处理降低了细胞活力、增殖和迁移能力，并抑制了HSFs的纤维化，而C-A1处理则产生相反的效果。BTA处理抑制了JAK2/STAT3信号通路。BTA降低了细胞活力、增殖和迁移能力，并抑制了HSFs的纤维化，而C-A1干预则削弱了BTA的作用。同时，BTA促进了体内伤口愈合并减少了胶原沉积。综上所述，BTA抑制JAK2/STAT3信号通路，进而阻碍HSFs的增殖、迁移和纤维化，并促进小鼠伤口愈合。
