5-FU诱发小鼠气管上皮损伤修复过程及其基因芯片解析  

The Recovery Process of Murine Tracheal Epithelium Injured by 5-FU and Its Microarray Analysis

作　　者：张菁茹[1] 宋楠[1] 贾心善[1] 孙善亮[1] 马小波[1] 王恩华[1] 

机构地区：[1]中国医科大学基础医学院病理学教研室,中国医科大学附属第一医院病理科,沈阳110001

出　　处：《中国肺癌杂志》2009年第2期106-110,共5页Chinese Journal of Lung Cancer

基　　金：国家自然科学基金(N0.30170407)资助~~

摘　　要：背景与目的虽然气管干细胞的定位研究有较大进步,但其增殖分化调节机制至今不清。方法本研究应用形态学、免疫荧光、基因芯片等方法观察及分析5-FU诱发小鼠离体气管上皮损伤修复过程,探讨气管干细胞增殖分化调节机制。结果因5-FU作用气管上皮进入增殖期分化细胞坏死、脱落,基底膜上仅残留少数G0期细胞,放回普通培养液后,气管上皮变扁平、以后呈立方,以至恢复气管上皮。这些G0期细胞显示干细胞标志ABCG2阳性,表明为未分化细胞,能分化成纤毛细胞及Clara细胞,说明具有干细胞多分化能力。采用干细胞基因芯片比较在恢复24h及48h与正常气管上皮基因表达的差异。24h后差异基因8个上调,31个下调。48h后5个上调,42个下调。差异基因表达主要集中在细胞周期调控、细胞连接、FGF、BMP分子、Notch、Wnt信号通路上。结论差异基因表达与气管干细胞增殖分化调控机制关系密切。Background and objective Although there are increasing reports on localization of tracheal stem cells, the mechanism of proliferation and differentiation of tracheal stem cells remains unclear. Methods In this study, we developed an ex viro model of murine tracheal epithelial injury and regeneration induced by 5-FU. The regeneration process of murine tracheal epithelium was observed and analyzed by morphological, immunofluorescence and microarray methods, Results After treatment with 5-FU, the differentiated mature cells were dead and desquamated. Only a few cells remained in Go phase and located on the basement membrane. After being put back in normal culture media, the cells became flat, cubic and restored as pseudostratified epithelium at last. These Go phase cells were ABCG2 positive. We detected the differences of stem cell genes between normal tracheal epithelial cells and regenerated epithelial cells at 24 h and 48 h after injured by 5-FU using stem cell differentiation gene microarray. At 24 h, 8 genes were up-regulated and 31 genes were down-regulated. At 48 h, 5 genes were up-regulated and 42 genes were down-regulated. Conclusion The differently expressed genes were mainly associated with cell cycle regulation, intercellular junction, FGF, BMP, Notch and Wnt signaling pathways, which suggested these alterations might be closely associated with the proliferation and differentiation of tracheal stem cells.

关 键 词：气管 干细胞 分化 基因芯片 信号通路 

分 类 号：R562[医药卫生—呼吸系统]