| 王晓芬,李福祥,黎俊雅,朱忠立,祝国芸.靶向沉默HIF-1α信号通路抑制百草枯中毒诱导的肺泡上皮细胞上皮间质转化[J].现代生物医学进展英文版,2018,(13):2419-2423. |
| 靶向沉默HIF-1α信号通路抑制百草枯中毒诱导的肺泡上皮细胞上皮间质转化 |
| Paraquat Promotes Epithelial-mesenchymal Transition of Alveolar Epithelial Cells through HIF-1α Signaling Pathway |
| Received:November 26, 2017 Revised:December 25, 2017 |
| DOI：10.13241/j.cnki.pmb.2018.13.004 |
| 中文关键词: 百草枯 肺纤维化 缺氧诱导因子-1A 上皮-间质转化 |
| 英文关键词: Paraquat Pulmonary fibrosis HIF-1α Epithelial--mesenchymal transition |
| 基金项目:国家自然科学基金项目（81170281） |
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| 中文摘要: |
| 摘要 目的：探讨HIF-1α信号通路在百草枯( paraquat, PQ) 诱导大鼠Ⅱ型肺泡上皮细胞上皮间质转化(Epithelial-mesenchymal tran- sition, EMT)中的作用机制。方法：使用20 μmol /L浓度的百草枯溶剂对大鼠Ⅱ型肺泡上皮RLE-6TN细胞干预24 h，随后在倒置光学显微镜观察各组细胞形态学变化；用real-time PCR与Western blot法检测RLE-6TN细胞中HIF-1α、上皮表型标记蛋白E-cadherin及间质表型标记蛋白Vimentin的表达，Transwell侵袭实验检测各处理组细胞侵袭能力的改变；使用HIF-1α靶向siRNA抑制其表达后，进一步采用RT-PCR和Western blot检测HIF-1α、E-cadherin和Vimentin的表达水平，Transwell法检测细胞侵袭能力变化。结果：体外百草枯溶液可显著诱导大鼠Ⅱ型肺泡上皮细胞RLE-6TN细胞HIF-1α表达升高和上皮间质转化的发生，同时细胞的体外侵袭能力也增强。靶向沉默HIF-1α基因后，百草枯诱导的上皮间质转化过程被逆转，同时细胞侵袭能力显著减弱。结论：百草枯通过调控HIF-1α信号通路来诱导RLE-6TN细胞上皮间质转化的发生，进而促进肺纤维化的形成。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of HIF-1α signaling pathway on paraquat (PQ)-induced epithelial-mesenchymal transition (EMT) in rat alveolar type II cells (RLE-6TN) and explore the underlying molecular mechanisms. Methods: RLE-6TN cells were treated by 20 μmol /L PQ, then the morphology was observed by invert light microscope; RT-PCR and Western blot were per- formed to detect the expression level of EMT related markers, E-cadherin and vimentin as well as HIF-1α signaling. Then the Transwell invasion assays was performed to detect the ability of cell invasion. Results: PQ was able to induce the transition of RLE-6TN cells from epithelial morphology to fibroblast-like morphology, associated with the acquisition of migratory properties. Phenotypically, PQ in- duced-EMT was characterized by loss of epithelial cell markers including E-cadherin, while upregulation of mesenchymal cell markers including vimentin, concurrent with the activation of HIF-1α signaling pathway. Furthermore, knockdown of HIF-1α by using specific siRNA could reverse PQ triggered EMT process and attenuated cell migration ability. Conclusion: PQ promoted EMT in rat alveolar type II cells (RLE-6TN) by upregulating the expression of HIF-1α. |
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