地塞米松抑制转化生长因子β_1对人α_1(Ⅰ)前胶原基因的转录激活

Dexamethasone inhibits the promoter activities of human α_1(I) procollagen gene induced by transforming growth factor β_1

目的 探讨地塞米松与转化生长因子 β1 (TGFβ1 )之间的相互作用及对人α1 (Ⅰ )前胶原基因启动转录的影响。方法 人皮肤及瘢痕成纤维细胞原代、传代培养。采用FuGENE转染试剂 ,分别瞬间转染含人α1 (Ⅰ )胶原基因 5′侧翼序列 - 2 5kb与报告基因氯霉素乙酰基转移酶 (CAT)的重组体 phCOL2 5至人皮肤及瘢痕成纤维细胞。ELISA法测定地塞米松及TGFβ1 作用 2 4h后 ,转染了phCOL2 5的 2种成纤维细胞的报告基因CAT表达量。 结果 地塞米松能抑制转染了 phCOL2 5重组体的人皮肤及瘢痕成纤维细胞CAT表达量 ,且能拮抗TGFβ1 对转染了 phCOL2 5重组体的 2种成纤维细胞CAT表达的上调作用 (P <0 0 5)。结论 在正常皮肤及瘢痕成纤维细胞中 ,地塞米松均能抑制人α1 (Ⅰ )前胶原基因的启动转录 ,且能拮抗TGFβ1 对人α1 (Ⅰ )

Objective To investigate the effects of dexamethasone on the promoter activities of human α 1(Ⅰ) procollagen gene induced by TGF β 1.Methods Fibroblasts from human skin and hypertrophic scar were primary cultured and subcultured.Cells were transiently transfected with plasmid phCOL2 5,containing -2 5kb of 5flank sequence of human α 1(Ⅰ) procollagen gene,fused to CAT reporter gene by FuGENE Transfection reagent.The effects of dexamethasone and TGF β 1 on the fibroblasts transfected with phCOL2 5 were determined by CAT ELISA.Results Dexamethasone not only reduced the CAT expression of fibroblasts transfected with phCOL2 5 but also inhibited the CAT expression up regulated by TGF β 1 in normal and hypertrophic scar fibroblasts ( P< 0 05).Conclusion Dexamethasone can down regulate basal and TGF β 1 induced promoter activities of human α 1(Ⅰ) procollagen gene in normal and hypertrophic scar fibroblasts.