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  • 张楚怡,李姝君,黄小玲,等.YY1对肺泡Ⅰ型上皮细胞纤维化的调控研究[J].同济大学学报(医学版),2018,39(5):5-10.    [点击复制]
  • ZHANG Chu-yi,LI Shu-jun,HUANG Xiao-ling,et al.The role of YY1 during fibrosis in alveolar type Ⅰ epithelial cells and the related mechanisms[J].同济大学学报(医学版),2018,39(5):5-10.   [点击复制]
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YY1对肺泡Ⅰ型上皮细胞纤维化的调控研究
张楚怡,李姝君,黄小玲,赵倩,林忻,俞作仁
0
(同济大学附属东方医院转化医学研究中心,上海200120; 大连医科大学基础医学院,大连116044;甘肃省人民医院药剂科,兰州730000)
摘要:
目的 研究核转录因子YinYang1(YY1)对肺泡Ⅰ型上皮细胞的调控功能及作用机制。方法 比较不同肺泡上皮细胞和肺癌细胞中纤维化标志物分子和YY1的表达;通过CCK8增殖实验检测YY1对R3/1细胞增殖的影响;通过YY1过表达以及特异敲低技术,检测TGF-β1刺激R3/1细胞后纤维化标志物分子的表达;通过Western印迹法检测YY1影响NF-κB质核转移的作用。结果 纤维化标志物分子α-sma和vimentin在R3/1细胞中特异高表达,与A549细胞相比,YY1在R3/1细胞中低表达;YY1显著抑制R3/1细胞增殖;过表达YY1降低TGF-β1诱导R3/1细胞中的α-sma和vimentin的表达,敲低YY1能够进一步促进TGF-β1诱导的α-sma高表达;在R3/1细胞中过表达YY1抑制TGF-β1诱导的NF-κB细胞核蛋白增加。结论 YY1在R3/1细胞中能够抑制TGF-β1诱导的NF-κB从细胞质到细胞核的转移,进而抑制了其对纤维化基因的转录激活。
关键词:  特发性肺纤维化  肺泡Ⅰ型上皮细胞  YinYang1
DOI:10.16118/j.1008-0392.2018.05.002
投稿时间:2018-05-05
基金项目:国家自然科学基金面上项目(81370175)
The role of YY1 during fibrosis in alveolar type Ⅰ epithelial cells and the related mechanisms
ZHANG Chu-yi,LI Shu-jun,HUANG Xiao-ling,ZHAO Qian,LIN Xin,YU Zuo-ren
(Translation Stem Cell Research Center, East Hospital, Tongji University, Shanghai 200120, China;Translation Stem Cell Research Center, East Hospital, Tongji University, Shanghai 200120, China; College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China;;Translation Stem Cell Research Center, East Hospital, Tongji University, Shanghai 200120, China; Dept. of Pharmacy, Gansu Provincial Hospital, Lanzhou 730000, China)
Abstract:
Objective To investigate the effects of nuclear transcription factor YY1 on alveolar type Ⅰ epithelial cells(type Ⅰ AEC) and its mechanisms. Methods The expression of fibrosis markers and YY1 were compared in different types of alveolar epithelial cells and lung cancer cells. The effect of YY1 on type Ⅰ AEC R3/1 cell proliferation was examined by CCK8 assay. The expression of fibrosis markers was determined by Western blotting and qRT-PCR in R3/1 cells with over-expressed or knockdowned YY1 and TGF-β 1. The expression of NF-κB protein in the cytoplasm and the nucleus was also detected by Western blot in R3/1 cells transfected with TGF-β and YY1 plasmid. Results Compared with type Ⅱ AEC A549 cells, the expression of fibrotic markers α-sma and vimentin was significantly higher and the expression of YY1 was significantly lower in R3/1 cells. Over-expression of YY1 reduced α-sma mRNA and protein expression in R3/1 cells after TGF-β1 treatment, while YY1 knockdown promoted the α-sma induction in TGF-β treated R3/1 cells. Overexpression of YY1 reduced the expression of nuclear protein of NF-κB, which was induced by TGF-β1 in R3/1 cells. Conclusion YY1 can inhibit the relocalization of NF-κB from the cytoplasm to the nucleus induced by TGF-β1 in R3/1 cells, which is associated with the inhibition of transcriptional activation of fibrosis-related genes.
Key words:  pulmonary fibrosis  type Ⅰ alveolar epithelial cell  YY1

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