Effects of bromodomain containing protein 4 specific inhibitor JQ-1 on human hypertropic scar
10.3969/j.issn.1674-8115.2017.07.007
- VernacularTitle:溴结构域蛋白4特异性抑制剂JQ-1对人增生性瘢痕的影响
- Author:
Yange HU
;
Jian HAO
;
Di ZHANG
;
Chuanfeng YANG
;
Chenlu SONG
;
Yong FANG
- Keywords:
hypertrophic scar;
scar fibroblast;
bromodomain containing protein 4;
JQ-1
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2017;37(7):924-929
- CountryChina
- Language:Chinese
-
Abstract:
Objective·To investigate effect and the possible molecular mechanism of JQ1,a specific inhibitor of bromodomain containing protein 4,on human hypertropic scar.Methods·Primary fibroblasts were isolated from human hypertrophic scars and treated with JQ-1 of different concentrations (0.1,0.5,1.0,2.0,2.5,and 12.5μmol/L) for 48 h.Then CCK-8 kit and wound healing assay were used to measure proliferation and migration of the fibroblasts.ELISA was adopted to detect the levels of collagen type Ⅰ (COL Ⅰ) and TGF-β1 after JQ-1 treatment for 24 h.Thirty-six nude mice were used for hypertrophic scar models.Human hypertrophic scars (1.0 cm× 1.0 cm×0.5 cm) were grafted subcutaneously at the backs of nude mice to establish scar animal models.After 4 weeks,the nude mice were averagely divided into two groups,i.e.JQ-1 group and DMSO group,which were respectively injected with 0.5 μmol/L JQ-1 and 0.1％ DMSO each mouse every day.COL Ⅰ / Ⅲ and α-smooth muscle actin (α-SMA) were examined by immunohistochemical method and sirius red staining.Results·Cell experiments showed that JQ-1 with the concentration of 0.5 μmol/L and above significantly inhibited proliferation of fibroblasts (P＜0.01).JQ-1 inhibited migration of fibroblast (P＜0.01).JQ-1 inhibited secretion of COL Ⅰ and TGF-β1 of fibroblasts (P＜0.01).Animal experiments showed that concentration and proportion of COL Ⅰ / Ⅲ in JQ-1 group decreased compared to DMSO group (P＜0.05).α-SMA protein expression in JQ-1 group also decreased (P＜0.05).Conclusion·JQ-1 can inhibit proliferation,migration,secretion of COL Ⅰ,and production of TGF-β1 of human sear fibroblasts in vitro;it can also inhibit secretion of COL Ⅰ /Ⅲ and fibroblast-myofibroblast differentiation in the human hypertrophic scars in nude mice.
