PCBs暴露ApoE-/-小鼠肝脏的microRNA和mRNA调控网络研究

黄风尘, 单秋丽, 王静, 杜宇国. PCBs暴露ApoE-/-小鼠肝脏的microRNA和mRNA调控网络研究[J]. 环境化学, 2014, 33(10): 1768-1775. doi: 10.7524/j.issn.0254-6108.2014.10.001
引用本文: 黄风尘, 单秋丽, 王静, 杜宇国. PCBs暴露ApoE-/-小鼠肝脏的microRNA和mRNA调控网络研究[J]. 环境化学, 2014, 33(10): 1768-1775. doi: 10.7524/j.issn.0254-6108.2014.10.001
HUANG Fengchen, SHAN Qiuli, WANG Jing, DU Yuguo. MicroRNA-mRNa interaction network in the liver of ApoE-/- mice exposed to PCBs[J]. Environmental Chemistry, 2014, 33(10): 1768-1775. doi: 10.7524/j.issn.0254-6108.2014.10.001
Citation: HUANG Fengchen, SHAN Qiuli, WANG Jing, DU Yuguo. MicroRNA-mRNa interaction network in the liver of ApoE-/- mice exposed to PCBs[J]. Environmental Chemistry, 2014, 33(10): 1768-1775. doi: 10.7524/j.issn.0254-6108.2014.10.001

PCBs暴露ApoE-/-小鼠肝脏的microRNA和mRNA调控网络研究

  • 基金项目:

    国家自然科学基金(21077127)

    国家重点基础研究发展计划(2009CB421605)资助.

MicroRNA-mRNa interaction network in the liver of ApoE-/- mice exposed to PCBs

  • Fund Project:
  • 摘要: 本研究通过microRNA-mRNA相互作用考察PCBs的基因毒性, 探讨PCBs致动脉粥样硬化可能的分子机制.研究使用8周龄ApoE-/-小鼠,腹腔注射PCBs混合物Aroclor1254(55 mg·kg-1体重),暴露6周后获取其肝脏,提取总RNA,获取cDNA或对RNA去磷酸化及特征标记.采用Affymetrix GeneChip® Mouse Genome 430 2.0 基因芯片和Agilent Mouse microRNA array芯片,分析Aroclor1254暴露前后mRNAs和miRNAs的差异表达情况.随后,结合Affymetrix mRNA芯片平台,使用IPA软件分析差异表达的miRNAs和mRNAs,揭示Aroclor1254暴露对基因调控网络和信号通路的影响.研究结果显示,Aroclor1254暴露后有18个差异表达的miRNAs能够靶向调控110个差异表达的mRNAs,二者可共同影响糖代谢、脂代谢、细胞死亡、分子运输等生物学功能.进一步考察与动脉粥样硬化发生发展密切相关的糖代谢、脂代谢网络调控,发现miRNA-22、let-7family、miRNA-15a/b,以及靶基因PPARα、PPARγ辅助激活因子1α和Foxo1,在PCBs暴露致动脉粥样硬化发生发展的糖脂代谢异常中发挥了重要作用.
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  • [1] Filipowicz W,Bhattacharyya S N,Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight?[J].Nature Reviews Genetics,2008,9(2):102-114
    [2] Bartel D P. MicroRNAs:Genomics,biogenesis,mechanism,and function[J].Cell,2004,116(2):281-297
    [3] Friedman R C,Farh K K,Burge C B,et al. Most mammalian mRNAs are conserved targets of microRNAs[J].Genome Research,2009,19(1):92-105
    [4] Santovito D,Mezzetti A,Cipollone F. MicroRNAs and atherosclerosis:New actors for an old movie[J].Nutrition,Metabolism,and Cardiovascular Diseases:NMCD,2012,22(11): 937-943
    [5] Madrigal-Matute J,Rotllan N,Aranda J F,et al. MicroRNAs and atherosclerosis[J].Current Atherosclerosis Reports,2013,15(5):322
    [6] Siasos G,Kollia C,Tsigkou V,et al. MicroRNAs:Novel diagnostic and prognostic biomarkers in atherosclerosis[J].Current Topics in Medicinal Chemistry,2013,13(13):1503-1517
    [7] Hu S S,Kong L Z,Gao R L,et al. Outline of the report on cardiovascular disease in China,2010[J].Biomedical and Environmental Sciences:BES,2012,25(3):251-256
    [8] Birnbaum L S. Endocrine effects of prenatal exposure to PCBs,dioxins,and other xenobiotics-implications for policy and future-research[J].Environmental Health Perspectives,1994,102(8):676-679
    [9] Letcher R J,Bustnes J O,Dietz R,et al. Exposure and effects assessment of persistent organohalogen contaminants in arctic wildlife and fish[J].Science of the Total Environment,2010,408(15):2995-3043
    [10] Imamura T,Kanagawa Y,Matsumoto S,et al. Relationship between clinical features and blood levels of pentachlorodibenzofuran in patients with Yusho[J].Environmental Toxicology,2007,22(2):124-131
    [11] Kouznetsova M,Huang X,Ma J,et al. Increased rate of hospitalization for diabetes and residential proximity of hazardous waste sites[J].Environmental Health Perspectives,2007,115(1):75-79
    [12] Hennig B,Oesterling E,Toborek M. Environmental toxicity,nutrition,and gene interactions in the development of atherosclerosis[J].Nutrition,Metabolism,and Cardiovascular Diseases:NMCD,2007,17(2):162-169
    [13] Huang X,Lessner L,Carpenter D O. Exposure to persistent organic pollutants and hypertensive disease[J].Environmental Research,2006,102(1):101-106
    [14] Uemura H. Associations of exposure to dioxins and polychlorinated biphenyls with diabetes: based on epidemiological findings[J].Nippon Eiseigaku Zasshi(Japanese Journal of Hygiene),2012,67(3):363-374
    [15] Lee D H,Lind L,Jacobs D R,et al. Associations of persistent organic pollutants with abdominal obesity in the elderly:The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study[J].Environment International,2012,40:170-178
    [16] Gustavsson P,Hogstedt C. A cohort study of Swedish capacitor manufacturing workers exposed to polychlorinated biphenyls (PCBs)[J].American Journal of Industrial Medicine,1997,32(3):234-239
    [17] Sergeev A V,Carpenter D O. Hospitalization rates for coronary heart disease in relation to residence near areas contaminated with persistent organic pollutants and other pollutants[J].Environmental Health Perspectives,2005,113(6):756-761
    [18] Watkins B A,Hannon K,Ferruzzi M,et al. Dietary PUFA and flavonoids as deterrents for environmental pollutants[J].The Journal of Nutritional Biochemistry,2007,18(3):196-205
    [19] Kakela R,Kinnunen S,Kakela A,et al. Fatty acids,lipids,and cytochrome p-450 monooxygenase in hepatic microsomes of minks fed fish-based diets and exposed to Aroclor 1242[J].Journal of Toxicology and Environmental Health Part A,2001,64(5):427-446
    [20] Kamei M,Ohgaki S,Kanbe T,et al. Highly hydrogenated dietary soybean oil modifies the responses to polychlorinated biphenyls in rats[J].Lipids,1996,31(11):1151-1156
    [21] Bratberg M,Olsvik P A,Edvardsen R B,et al. Effects of oil pollution and persistent organic pollutants (POPs) on glycerophospholipids in liver and brain of male Atlantic cod (Gadus morhua)[J].Chemosphere,2013,90(7):2157-2171
    [22] Hou L,Wang D,Baccarelli A. Environmental chemicals and microRNAs[J].Mutation Research,2011,714(1/2):105-112
    [23] Guida M,Marra M L,Zullo F,et al. Association between exposure to dioxin-like polychlorinated biphenyls and miR-191 expression in human peripheral blood mononuclear cells[J].Mutation Research,2013,753(1):36-41
    [24] Zhu C,Yu Z B,Zhu J G,et al. Differential expression profile of micrornas during differentiation of cardiomyocytes exposed to polychlorinated biphenyls[J].International Journal of Molecular Sciences,2012,13(12):15955-15966
    [25] Reymann S,Borlak J. Transcriptome profiling of human hepatocytes treated with Aroclor 1254 reveals transcription factor regulatory networks and clusters of regulated genes[J].BMC Genomics,2006,7:217
    [26] Nash J T,Szabo D T,Carey G B. Polybrominated diphenyl ethers alter hepatic phosphoenolpyruvate carboxykinase enzyme kinetics in male Wistar rats: Implications for lipid and glucose metabolism[J].Journal of Toxicology and Environmental Health Part A,2013,76(2):142-156
    [27] Kutlu S,Colakoglu N,Halifeoglu I,et al. Comparative evaluation of hepatotoxic and nephrotoxic effects of aroclors 1221 and 1254 in female rats[J].Cell Biochemistry and Function,2007,25(2):167-172
    [28] Irizarry R A,Hobbs B,Collin F,et al. Exploration,normalization,and summaries of high density oligonucleotide array probe level data[J].Biostatistics,2003,4(2):249-264
    [29] Liu C G,Calin G A,Meloon B,et al. An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues[J].Proceedings of the National Academy of Sciences of the United States of America,2004,101(26):9740-9744
    [30] Thomson J M,Parker J,Perou C M,et al. A custom microarray platform for analysis of microRNA gene expression[J].Nature Methods,2004,1(1):47-53
    [31] Kersten S,Seydoux J,Peters J M,et al. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting[J].The Journal of Clinical Investigation,1999,103(11):1489-1498
    [32] Rosenson R S. Fenofibrate: Treatment of hyperlipidemia and beyond[J].Expert Review of Cardiovascular Therapy,2008,6(10):1319-1330
    [33] Iliopoulos D,Malizos K N,Oikonomou P,et al. Integrative microRNA and proteomic approaches identify novel osteoarthritis genes and their collaborative metabolic and inflammatory networks[J].PloS One,2008,3(11):e3740
    [34] Kaur K,Pandey A K,Srivastava S,et al. Comprehensive miRNome and in silico analyses identify the Wnt signaling pathway to be altered in the diabetic liver[J].Molecular BioSystems,2011,7(12):3234-3244
    [35] Zhang Y,Cheng X,Lu Z,et al. Upregulation of miR-15b in NAFLD models and in the serum of patients with fatty liver disease[J].Diabetes Research and Clinical Practice,2013,99(3):327-334
    [36] Bachman E S,Dhillon H,Zhang C Y,et al. BetaAR signaling required for diet-induced thermogenesis and obesity resistance[J].Science,2002,297(5582):843-845
    [37] Than T A,Lou H,Ji C,et al. Role of cAMP-responsive element-binding protein (CREB)-regulated transcription coactivator 3 (CRTC3) in the initiation of mitochondrial biogenesis and stress response in liver cells[J].The Journal of Biological Chemistry,2011,286(25):22047-22054
    [38] Frost R J,Olson E N. Control of glucose homeostasis and insulin sensitivity by the Let-7 family of microRNAs[J].Proceedings of the National Academy of Sciences of the United States of America,2011,108(52):21075-21080
    [39] Lee H,Park W J. Unsaturated Fatty acids,desaturases,and human health[J].Journal of Medicinal Food,2014,17(2):189-197
    [40] Puigserver P,Spiegelman B M. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): Transcriptional coactivator and metabolic regulator[J].Endocrine Reviews,2003,24(1):78-90
    [41] Sevane N,Armstrong E,Cortes O,et al. Association of bovine meat quality traits with genes included in the PPARG and PPARGC1A networks[J].Meat Science,2013,94(3):328-335
    [42] Esterbauer H,Oberkofler H,Linnemayr V,et al. Peroxisome proliferator-activated receptor-gamma coactivator-1 gene locus: Associations with obesity indices in middle-aged women[J].Diabetes,2002,51(4):1281-1286
    [43] Muller Y L,Bogardus C,Pedersen O,et al. A Gly482Ser missense mutation in the peroxisome proliferator-activated receptor gamma coactivator-1 is associated with altered lipid oxidation and early insulin secretion in Pima Indians[J].Diabetes,2003,52(3):895-898
    [44] Liang J,Liu C,Qiao A,et al. MicroRNA-29a-c decrease fasting blood glucose levels by negatively regulating hepatic gluconeogenesis[J].Journal of Hepatology,2013,58(3):535-542
    [45] Accili D,Arden K C. FoxOs at the crossroads of cellular metabolism,differentiation,and transformation[J].Cell,2004,117(4):421-426
    [46] Gross D N,van den Heuvel A P,Birnbaum M J. The role of FoxO in the regulation of metabolism[J].Oncogene,2008,27(16):2320-2336
    [47] Trajkovski M,Hausser J,Soutschek J,et al. MicroRNAs 103 and 107 regulate insulin sensitivity[J].Nature,2011,474(7353):649-653
    [48] Li F,Liu B,Gao Y,et al. Upregulation of MicroRNA-107 induces proliferation in human gastric cancer cells by targeting the transcription factor FOXO1[J].FEBS Letters,2014,588(4):538-544
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  • 收稿日期:  2014-03-11
黄风尘, 单秋丽, 王静, 杜宇国. PCBs暴露ApoE-/-小鼠肝脏的microRNA和mRNA调控网络研究[J]. 环境化学, 2014, 33(10): 1768-1775. doi: 10.7524/j.issn.0254-6108.2014.10.001
引用本文: 黄风尘, 单秋丽, 王静, 杜宇国. PCBs暴露ApoE-/-小鼠肝脏的microRNA和mRNA调控网络研究[J]. 环境化学, 2014, 33(10): 1768-1775. doi: 10.7524/j.issn.0254-6108.2014.10.001
HUANG Fengchen, SHAN Qiuli, WANG Jing, DU Yuguo. MicroRNA-mRNa interaction network in the liver of ApoE-/- mice exposed to PCBs[J]. Environmental Chemistry, 2014, 33(10): 1768-1775. doi: 10.7524/j.issn.0254-6108.2014.10.001
Citation: HUANG Fengchen, SHAN Qiuli, WANG Jing, DU Yuguo. MicroRNA-mRNa interaction network in the liver of ApoE-/- mice exposed to PCBs[J]. Environmental Chemistry, 2014, 33(10): 1768-1775. doi: 10.7524/j.issn.0254-6108.2014.10.001

PCBs暴露ApoE-/-小鼠肝脏的microRNA和mRNA调控网络研究

  • 1. 环境化学与生态毒理学国家重点实验室, 中国科学院生态环境研究中心, 北京, 100085
基金项目:

国家自然科学基金(21077127)

国家重点基础研究发展计划(2009CB421605)资助.

摘要: 本研究通过microRNA-mRNA相互作用考察PCBs的基因毒性, 探讨PCBs致动脉粥样硬化可能的分子机制.研究使用8周龄ApoE-/-小鼠,腹腔注射PCBs混合物Aroclor1254(55 mg·kg-1体重),暴露6周后获取其肝脏,提取总RNA,获取cDNA或对RNA去磷酸化及特征标记.采用Affymetrix GeneChip® Mouse Genome 430 2.0 基因芯片和Agilent Mouse microRNA array芯片,分析Aroclor1254暴露前后mRNAs和miRNAs的差异表达情况.随后,结合Affymetrix mRNA芯片平台,使用IPA软件分析差异表达的miRNAs和mRNAs,揭示Aroclor1254暴露对基因调控网络和信号通路的影响.研究结果显示,Aroclor1254暴露后有18个差异表达的miRNAs能够靶向调控110个差异表达的mRNAs,二者可共同影响糖代谢、脂代谢、细胞死亡、分子运输等生物学功能.进一步考察与动脉粥样硬化发生发展密切相关的糖代谢、脂代谢网络调控,发现miRNA-22、let-7family、miRNA-15a/b,以及靶基因PPARα、PPARγ辅助激活因子1α和Foxo1,在PCBs暴露致动脉粥样硬化发生发展的糖脂代谢异常中发挥了重要作用.

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