›› 2017, Vol. 37 ›› Issue (7): 924-.doi: 10.3969/j.issn.1674-8115.2017.07.007

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Effects of bromodomain containing protein 4 specific inhibitor JQ-1 on human hypertropic scar#br#

HU Yan-ge, HAO Jian, ZHANG Di, YANG Chuan-feng, SONG Chen-lu, FANG Yong   

  1. Department of Burn and Plastic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, China
  • Online:2017-07-28 Published:2017-08-25
  • Supported by:
    National Natural Science Foundation of China,81272081

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 12.5 μmol/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 scar fibroblasts in vitro; it can also inhibit secretion of COL Ⅰ / Ⅲ and fibroblast-myofibroblast differentiation in the human hypertrophic scars in nude mice.

Key words: hypertrophic scar, scar fibroblast, bromodomain containing protein 4, JQ-1