基于IPA分析自噬对大鼠肝再生中树突状细胞的调节作用

doi:10.16288/j.yczz.14-391

遗传 ›› 2015, Vol. 37 ›› Issue (3): 276-282.doi: 10.16288/j.yczz.14-391

基于IPA分析自噬对大鼠肝再生中树突状细胞的调节作用

王棋文^1,2,3,靳伟^1,2,3,常翠芳^1,2,3,徐存拴^1,2,3

1. 河南师范大学,河南省生物工程重点实验室,新乡 453007; 2. 河南师范大学,河南省-科技部共建细胞分化调控国家重点实验室培育基地,新乡 453007; 3. 河南师范大学生命科学学院,新乡453007

收稿日期:2014-11-13 修回日期:2015-01-12 出版日期:2015-03-20 发布日期:2015-02-10
通讯作者: 徐存拴,博士,教授,博士生导师,研究方向：肝再生的分子机理。E-mail: xucs@x263.net E-mail:wangqiwen@htu.edu.cn
作者简介:王棋文,博士研究生,研究方向：肝再生的分子机理。E-mail: wangqiwen@htu.edu.cn
基金资助:
河南省重大科技攻关项目(编号：111100910600),河南师范大学博士启动课题(编号：qd14175)和河南师范大学青年科学基金项目资助

Regulation of autophagy on dendritic cells during rat liver regeneration by IPA

Qiwen Wang^{1, 2, 3}, Wei Jin^{1, 2, 3}, Cuifang Chang^{1, 2, 3}, Cunshuan Xu^{1, 2, 3}

1. Key Laboratory for Bioengineering, Henan Normal University, Xinxiang 453007, China;
2. Co-construction Key Laboratory for Cell Differentiation and Regulation, Henan Normal University, Xinxiang 453007, China;
3. College of Life Science, Henan Normal University, Xinxiang 453007, China

Received:2014-11-13 Revised:2015-01-12 Online:2015-03-20 Published:2015-02-10

摘要/Abstract

摘要： 为探讨自噬对大鼠肝再生中树突状细胞(Dendritic cells, DCs)的调节作用,文章通过Percoll 密度梯度离心结合免疫磁珠分选分离大鼠DCs,Rat Genome 230 2.0芯片检测大鼠肝再生中自噬相关基因表达变化,利用IPA等软件分析自噬在DCs中的生理活动。结果表明,LC3、BECN1、ATG7和SQSTM1等关键基因在部分肝切除后不同恢复时间段有明显表达变化;芯片中对应的自噬相关基因为593个,其中210个基因发生了有意义的变化。比较分析自噬生理活动情况,发现自噬在再生早期和晚期阶段增强,增殖期减弱。与自噬相关的生理活动主要有RNA表达、RNA转录细胞分化和增殖,其中涉及的信号通路主要有PPARα/RXRα激活、急性期反应、TREM1 信号通路、IL-6 信号通路、IL-8 信号通路和IL-1 信号通路等,它们在肝再生阶段发生了不同程度的上调或下调。Cluster 分析还发现,P53和AMPK信号参与调控DCs的自噬活动,在肝再生早期主要是AMPK信号,在肝再生末期P53和AMPK信号共同参与自噬的调节。以上研究结果说明DCs自噬可能在肝再生早期激活细胞免疫反应和后期清除DCs等方面发挥着重要作用。

关键词: 肝再生, 自噬, 树突状细胞, Rat Genome 230 2.0 芯片, IPA

Abstract: To understand the mechanism underlying autophagy in regulating dendritic cells during rat liver regeneration, we used the method of percoll density gradient centrifugation combined with immunomagnetic bead to isolate dendritic cells, the Rat Genome 230 2.0 Array to determine the expression changes of autophagy-related genes, and Ingenuity Pathway Analysis 9.0 (IPA) to determine the autophagy activities. The results indicated that LC3, BECN1, ATG7 and SQSTM1 genes had significant expression changes during rat liver regeneration. There were 593 genes related to autophagy, among which 210 genes were identified as significant. We also showed that the activity of autophagy was enhanced in the priming phase and teminal phase of liver regeneration, weakened in the proliferative stage by comparative analysis method of IPA. The autophagy-related physiological activities mainly included RNA expression, RNA transcription, cell differentiation and proliferation, involving in PPARα/RXRα activation, acute phase response signaling, TREM1 signaling, IL-6 signaling, IL-8 signaling and IL-1 signaling, whose activities were increased or decreased in liver regeneration. Cluster analysis found that P53 and AMPK signaling participated in the regulation of dendritic cells autophagy, with AMPK signaling in the priming phase of liver regeneration, and both signaling pathways in the terminal phase. We conclude that dendritic cells autophagy played an important role in initiation of the immune response in priming phase and depletion of dendritic cells in late phase during rat liver regeneration.

Key words: rat liver regeneration, autophagy, dendritic cells, Rat Genome 230 2.0 Array, ingenuity pathway analysis

王棋文, 靳伟, 常翠芳, 徐存拴. 基于IPA分析自噬对大鼠肝再生中树突状细胞的调节作用[J]. 遗传, 2015, 37(3): 276-282.

Qiwen Wang, Wei Jin, Cuifang Chang, Cunshuan Xu. Regulation of autophagy on dendritic cells during rat liver regeneration by IPA[J]. HEREDITAS(Beijing), 2015, 37(3): 276-282.

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基于IPA分析自噬对大鼠肝再生中树突状细胞的调节作用

Regulation of autophagy on dendritic cells during rat liver regeneration by IPA

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