Inhibition of Notch signaling pathway reduces angiogenesis in hypertrophic scar.
10.11817/j.issn.1672-7347.2021.210234
- Author:
Songlian LI
1
;
Hongqiao FAN
2
;
Lifang LIU
3
;
Jie LING
4
;
Yuwei WU
4
Author Information
1. Graduate School, Hunan University of Chinese Medicine, Changsha 410208. 1459322595@qq.com.
2. Department of Breast Surgery, First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410007, China.
3. Department of Breast Surgery, First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410007, China. Liulff@126.com.
4. Graduate School, Hunan University of Chinese Medicine, Changsha 410208.
- Publication Type:Journal Article
- Keywords:
Notch signaling pathway;
angiogenesis;
hypertrophic scar
- MeSH:
Animals;
Cicatrix, Hypertrophic/pathology*;
Endothelial Cells;
Matrix Metalloproteinase 2;
Rats;
Rats, Sprague-Dawley;
Signal Transduction;
Transforming Growth Factor beta1;
Vascular Endothelial Growth Factor A
- From:
Journal of Central South University(Medical Sciences)
2021;46(11):1195-1202
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:Hypertrophic scar (HS) is the most common pathological scar in clinical practice. During its formation, angiogenesis-related factors show dynamic expression. Modern studies have found that Notch signaling pathway has an extremely important role in maintaining the construction and remodeling of vascular endothelial cells and vascular network. The correlation between Notch signaling pathway and angiogenesis in hypertrophic scar has been rarely reported. This study aims to investigate correlation between Notch signaling pathway and the expression of angiogenic factors in a proliferative scar model.
METHODS:A total of 81 Sprague Dawley rats (SPF grade) were randomly assigned into a blank control group, a model group, and a blocker group. In the blocker group, a 2 cm diameter circular scald head was placed on the back of the rats for 10 s at 75 ℃ by using a constant temperature and pressure electrothermal scalding apparatus to form a rat deep II° burn model, and a hyperplastic scar model rat was obtained after natural healing of the wound skin (21 to 23 day epithelialization). A syringe was used to inject a needle from the normal skin around the scar at the 1st, 3rd, 5th, 7th, and 14th days after modeling. The γ-secretase inhibitor was injected locally at 2 mg/kg in a dilution of 0.1 mL at the base of the scar. The rats in the model group was injected with the same amount of saline after modeling; the rats in the blank control group was injected with the same amount of saline. Nine rats in each group was randomly killed by air embolization at the 21st, 28th, and 35th days, respectively. The protein expressions of collagen type I (COL-I) and collagen type III (COL-III) were detected by immunohistochemistry. The protein expressions of vascular endothelial growth factor (VEGF), angiopoietin 1 (Ang1), transforming growth factor-β1 (TGF-β1), and matrix metalloproteinase-2 (MMP-2) were detected by Western blotting.
RESULTS:Immunohistochemical results showed that, at the 21st,28th, and 35th days, the protein expressions of COL-I and COL-III in the model group were up-regulated compared with the blank control group (all
CONCLUSIONS:In the Sprague Dawley rat proliferative scar model, inhibition of Notch signaling pathway could attenuate the expressions of COL-I and COL-III, reduce traumatic scar proliferation, down-regulate the expressions of VEGF, Ang1, TGF-β1, and MMP-2, and inhibit angiogenesis. The expressions of angiogenesis-related factors appeare to be up-regulated during the formation of proliferative scar. When the Notch signaling pathway is inhibited, the up-regulated angiogenic factors show a decreasing trend and the proliferative scar is alleviated, which suggests that Notch signaling pathway may affect the formation of hyperplastic scar by regulating the expression of angiogenic factors.
