Effects of bromodomain containing protein 4 specific inhibitor JQ-1 on human hypertropic scar / 上海交通大学学报（医学版）

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.