Roles of interleukin-6/signal transduction and activator of transcription 3 pathway and β-catenin in mechanical stress-induced hypertrophic scar formation in mice
10.3760/cma.j.cn501120-20200417-00231
- VernacularTitle:白细胞介素6/信号转导及转录激活因子3通路及β连环蛋白在机械应力致小鼠增生性瘢痕形成中的作用
- Author:
Lulu SHI
1
;
Rufeng ZHANG
;
Hu XIAO
Author Information
1. 山东第一医科大学附属省立医院烧伤整形外科,济南 250021
- Keywords:
Cicatrix;
Interleukin-6;
Phosphorylated signal transducer and activator of transcription 3;
β-catenin;
Mechanical stress
- From:
Chinese Journal of Burns
2021;37(7):647-653
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To establish mechanical stress-induced hypertrophic scar mouse models, and to examine the roles of interleukin-6/signal transduction and activator of transcription 3 (IL-6/STAT3) pathway and β-catenin.Methods:The experimental research method was used. Sixteen female C57/BL6 mice of 12-week-old were collected and two straight full-thickness skin incisions of 2 cm in length were inflicted on the back of each mouse. On the fourth day post injury, the two wounds on the back of each mouse were divided into mechanical traction group and blank control group according to the random number table method, with 16 wounds in each group. The wounds in mechanical traction group were given continuous mechanical traction for 14 days, while the wounds in blank control group were given no treatment. After 14 days of mechanical traction for wounds in mechanical traction group, the appearances of the scar tissue in wounds of 2 groups were visually observed, and the areas of scars were measured; the morphological changes of the scar tissue in wounds of 2 groups were observed by hematoxylin-eosin staining, and the cross-sectional areas of scars were measured; the content of IL-6 in supernatant of the scar tissue in wounds of 2 groups was detected by enzyme-linked immunosorbent assay; the protein expression of phosphorylated STAT3 (p-STAT3) of the scar tissue in wounds of 2 groups was detected by Western blotting; and the expression of β-catenin of the scar tissue in wounds of 2 groups was detected by immunohistochemistry. Data were statistically analyzed with paired sample t test. Results:Red hairless area similar to human scar tissue formed in wounds of mechanical traction group after 14 days of mechanical traction, with large area of scar, thickened local area, hardened texture, and some even slightly raised, while scar in wounds of blank control group was linear and not obvious. After 14 days of mechanical traction for wounds in mechanical traction group, the scar area of wounds in mechanical traction group was (5.65±0.95) mm 2, which was significantly larger than (1.07±0.28) mm 2 in blank control group ( t=26.333, P<0.01). After 14 days of mechanical traction for wounds in mechanical traction group, the skin appendages of scar tissue were absent, and the dermis hyperplasia was active and obviously thickened, while skin appendages of scar tissue of wounds in blank control group were still present, with unconspicuous dermis hyperplasia; the cross-sectional area of scar in wounds of mechanical traction group was (0.82±0.23) mm 2, which was significantly larger than (0.29±0.07) mm 2 of blank control group ( t=8.879 , P<0.01). After 14 days of mechanical traction for wounds in mechanical traction group, the content of IL-6 in the supernatant of scar tissue and the protein expression of p-STAT3 in scar tissue of wounds in mechanical traction group were significantly higher than those in blank control group ( t=37.552, 25.863, P<0.01). The expression of β-catenin was high in the scar tissue of wounds in mechanical traction group after 14 days of mechanical traction, while that in blank control group was low. Conclusions:The study successfully establishes mechanical stress-induced hypertrophic scar mouse models. Mechanical stress can participate in wound healing and induce scar hyperplasia of mice wounds through continuous or overexpression of IL-6/STAT3 pathway, and β-catenin can also promote the formation of hypertrophic scar.