E1A激活基因阻遏子基因表达与血管外膜成纤维细胞表型转化的关系The change of cellular repressor of E1A-stimulated genes during adventitial fibroblast phenotypic switching
李洋,韩雅玲,闫承慧
摘要(Abstract):
目的探讨E1A激活基因阻遏子(CREG)基因表达与血管外膜成纤维细胞(AFs)表型转化间的关系。方法制作小鼠颈动脉损伤模型,免疫荧光染色观察血管外膜中CREG与平滑肌肌动蛋白(α-SMA)表达变化;培养小鼠原代AFs,外源性应用血管紧张素Ⅱ(AngⅡ)诱导其表型转化,RT-PCR和Western-blot检测不同作用时间及不同浓度AngⅡ刺激AFs后CREG和α-SMA mRNA和蛋白质表达。结果血管损伤后1 d、3 d血管外膜增生显著,外膜中α-SMA表达显著上调,而CREG表达显著下调;血管损伤后7 d、14 d外膜增生有所缓解,α-SMA表达水平逐渐下降,而CREG表达也有所恢复。应用AngⅡ诱导AFs发生表型转化,AFs中α-SMA mRNA和蛋白水平显著上调,而CREG mRNA和蛋白水平显著下调,并且呈时间和剂量依赖性。结论在体和离体模型均表明AFs表型转化过程中伴随CREG基因表达下调,提示CREG基因可能参与AFs的表型转化。
关键词(KeyWords): E1A激活基因阻遏子;血管外膜成纤维细胞;表型转化
基金项目(Foundation): 国家自然科学基金项目(81130072,81370243);; 国家重点基础研究发展计划(973计划2012CB517804);; 科技部重大新药创制创新药物研究开发技术平台建设(GCP)(2012ZX09303016-002)
作者(Author): 李洋,韩雅玲,闫承慧
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