| 宋文文 张华 高岱清 孙荣丽 张春玲.EGFR 信号通路在SiO2诱导肺上皮细胞间质转化中的作用机制[J].,2014,14(19):3646-3650 |
| EGFR 信号通路在SiO2诱导肺上皮细胞间质转化中的作用机制 |
| Roles of EGFR Signaling Pathway in Silica-induced Epithelial-mesenchymalTransition in Human A549 cells |
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| DOI： |
| 中文关键词: 表皮生长因子受体 矽尘 A549 细胞 上皮间质转化 |
| 英文关键词: EGFR SiO2 A549 cell Epithelial-mesenehymal transition |
| 基金项目:青岛市民生计划项目（[d1]2013-1-3-47-nsh） |
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| 中文摘要: |
| 目的：在二氧化硅（SiO2）刺激下可引起肺部一系列的炎症反应及其伴随相关的成纤维细胞增殖，然而EGFR信号通路可维
持细胞增殖、分化和凋亡的平衡，因此，我们可以设想EGFR信号通路是否在肺纤维化的发生发展中起到重要的作用。本实验探
讨SiO2是否能诱导人肺上皮细胞（A549）发生上皮间质转化，并且研究EGFR 信号通路在矽肺纤维化中的作用机制。方法：以
A549 为研究对象，用0（对照组）、50、100、200 ug/ml SiO2孵育A549，作用48h 后于倒置显微镜观察细胞形态学改变，并收集不同
时段细胞，采用实时荧光定量PCR（RT-PCR）检测E-钙黏蛋白(E-cadherin)和alpha- 平滑肌肌动蛋白(alpha-SMA) mRNA表达变化，细胞
免疫荧光方法检测E-cadherin、alpha-SMA 及信号转导蛋白EGFR 表达的变化。结果：倒置显微镜观察A549 经SiO2处理后细胞形态
由鹅卵石状转变为纺锤型或梭型，形态似成纤维细胞，随着SiO2浓度的升高，E-cad mRNA和蛋白表达逐渐下调，在200 ug /ml 组
表达最低，琢-SMA mRNA和蛋白表达逐渐上调，200 ug /ml组琢-SMA表达最高；EGFR 蛋白表达上调；50、100、200 ug/ml 与对照
组的差异具有统计学学意义（P<0.05）。结论：SiO2可诱导肺上皮细胞向间质细胞转化，其机制可能与EGFR 信号通路有关。 |
| 英文摘要: |
| Objective:Silica exposure results in an initially acute lung inflammatory response followed by the proliferation of
fibroblasts. The epidermal growth factor receptor (EGF-R) signaling pathway maintains a balance between cell proliferation,
differentiation and apoptosis, and thus it is imagined that EGF-R signaling pathways play an important role in the development and
progression of Pulmonary fibrosis. To investigate silica-induced Epithelial-mesenehymal transition (EMT) in human A549 cells and the
roles of EGFR signaling pathway in silica-induced EMT in Human A549 cells in vitro.Methods:A549 cells were cultured and stimulated
with indicated doses of silica (0, 50, 100, 200 ug/ml). The cells morphology changes were observed under phase-constrast microscope. In
addition, The mRNA level of E-cadherin and a-SMA were also evaluated by Real-time PCR(qRT-PCR). The protein level of E-cadherin,
a-SMA and EGFR were assessed by immunnoflurescence staining.Results:The data showed that silica-induced A549 cells with
epithelial cell characteristics to undergo EMT in a dose-dependent manner. After exposure to silica, A549 cells induced EMT
characterized by cells morphological changes, such as displayed a spindle-shape, fibroblast-like morphology. Compared with the control,
the expression of E-cad mRNA and protein in silica-induced A549 cells was significantly down-regulated; The expression of a-SMA
mRNA and protein in silica-induced A549 cells was significantly up-regulated. Compared with the control group, the activation of EGFR
was obvious in silica-stimulated A549 cells (P<0.05).Conclusion:Silica might induce EMT in human A549 cells indirectly, and the
mechanismis most likely associated with the activation of EGFR signaling pathway. |
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