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BPA暴露对本体和子代胰岛β细胞转录组差异对比分析

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姬晓彤, 岳慧峰, 武美琼, 白剑英. BPA暴露对本体和子代胰岛β细胞转录组差异对比分析[J]. 环境化学, 2021, (2): 509-519. doi: 10.7524/j.issn.0254-6108.2020101306
引用本文: 姬晓彤, 岳慧峰, 武美琼, 白剑英. BPA暴露对本体和子代胰岛β细胞转录组差异对比分析[J]. 环境化学, 2021, (2): 509-519. doi: 10.7524/j.issn.0254-6108.2020101306
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JI Xiaotong, YUE Huifeng, WU Meiqiong, BAI Jianying. Analysis of the differences of BPA exposure on the transcriptome of islet cells between adults and offspring[J]. Environmental Chemistry, 2021, (2): 509-519. doi: 10.7524/j.issn.0254-6108.2020101306
Citation: JI Xiaotong, YUE Huifeng, WU Meiqiong, BAI Jianying. Analysis of the differences of BPA exposure on the transcriptome of islet cells between adults and offspring[J]. Environmental Chemistry, 2021, (2): 509-519. doi: 10.7524/j.issn.0254-6108.2020101306
shu

BPA暴露对本体和子代胰岛β细胞转录组差异对比分析

  • 1. 山西医科大学公共卫生学院环境卫生教研室, 太原, 030001;

  • 2. 山西大学环境与资源学院环境健康研究中心, 太原, 030006

    • 通讯作者: 白剑英, E-mail: jybai66@sxmu.edu.cn
  • 基金项目:

    国家自然科学基金（21906099），山西省教育厅高校科技创新项目（2020L0174，2020L0025）和山西省自然科学基金（201701D121140）资助.

Analysis of the differences of BPA exposure on the transcriptome of islet cells between adults and offspring

  • 1. Department of Environmental Health, School of Public Health, Shanxi Medical University, Taiyuan, 030001, China;

  • 2. College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, 030006, China

    • Corresponding author: BAI Jianying, jybai66@sxmu.edu.cn
  • Fund Project: Supported by National Natural Science Foundation of China(21906099),Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(2020L0174, 2020L0025)and Natural Science Foundation of Shanxi (201701D121140).

  • 摘要: 双酚A （BPA）作为一种典型的环境内分泌干扰物，与二型糖尿病和肥胖症等代谢类疾病密切相关.在这项研究中，旨在探讨BPA直接暴露以及围产期暴露对本体和子代胰岛β细胞影响的差异，从而实现对不同易感人群的精准预防与治疗.通过对GEO数据库中GSE126297和GSE82175两个数据集进行分析，共筛选出108个共有的差异基因，其中28个表达趋势一致，而另外80个表达趋势相反.随后对本体和子代单独的差异基因，以及共有差异基因进行了GO和KEGG对比分析.此外，利用String数据库和Cytoscape分析PPI网络中的紧密联系的基因，并将其可视化，进一步从28个表达趋势一致的基因中筛选出相互作用最为紧密的基因集1（Iqgap2，Igf2r和Rab18）；从80个表达趋势相反的基因中筛选出相互作用紧密的基因集2（Polr2f，Ccnt2，Polr2e，Kdm7a，Fbl）和基因集3（Atp5g2，Atp5o和Ndufa6）.最后，通过GEPIA在线验证上述基因在胰腺癌样本中的表达，研究发现Rab18，Polr2f，Polr2e，Fbl，Atp5g2，Atp5o和Ndufa6在胰腺癌病例中的表达均显著上升.同时，上述基因在本体中呈现显著上升趋势，而对于子代，只有Rab18显著上升，其他基因则呈下降趋势.综上，BPA对本体和子代的影响有一定的关联，其中关联的关键基因的异常表达可能会增加本体罹患胰腺癌的风险，而对于子代则会影响代谢过程和细胞结构.
    Abstract: Bisphenol-A (BPA) is a represent endocrine-disrupting chemical that has been proposed to be associated with type 2 diabetes and obesity. The present study aimed to investigate the differences between BPA direct exposure and maternal exposure on the transcriptome of islet cells in adults and offspring, and then to achieve accurate prevention and treatment of different sensitive population. By analyzing the two data sets of GSE126297 and GSE82175 collected from the GEO database, a total of 108 shared differentially expressed gene (DEG) between the two data sets were screened out, of which 28 showed the similar expression trend, while the other 80 showed the opposite expression trend. Subsequently, the GO and KEGG comparative analysis were carried out with the DEGs only in adult and offspring, and those DEGs in both groups. Then, PPI network and visualization was conducted using String database and Cytoscape software. the most closely interacting genes of gene set 1 (Iqgap2, Igf2r and Rab18) were screened from the 28 genes with the same expression trend, similarly genes of gene set 2 (Polr2f, Ccnt2, Polr2e, Kdm7a, Fbl) and those of gene set 3 (Atp5g2, Atp5o and Ndufa6) were screened from the 80 genes with opposite trend. Finally, GEPIA was used to verify the expression levels of these genes in pancreatic cancer samples, the results showed that Rab18, Polr2f, Polr2e, Fbl, Atp5g2, Atp5o and Ndufa6 was increased significantly in pancreatic cancer. In addition, these genes also showed a significant increase in adult; as for the offspring, only Rab18 increased significantly, while other genes showed a downward trend. Taken together, the influence of BPA on adult is related to that on the offspring. The abnormally expressed key genes may increase the risk of pancreatic cancer of adult, and affect the metabolic process and cell structure of the offspring.
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  • [1] WHO. Obesity and overweight[EB/OL].[2020-9-28]. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
    [2] COVACI A, DEN Hond E, GEENS T, et al. Urinary BPA measurements in children and mothers from six European member states:Overall results and determinants of exposure[J]. Environ Res, 2015, 141:77-85.
    [3] USFDA. Bisphenol A (BPA):Use in Food Contact application[EB/OL].[2021-1-24]. https://www.fda.gov/food/food-additives-petitions/bisphenol-bpa-use-food-contact-application
    [4] EC. Commission Directive 2011/8/EU of 28 January 2011 amending Directive 2002/72/EC as regards the restriction of use of Bisphenol A in plastic infant feeding bottles[EB/OL].[2020-9-6]. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32011L0008&from=DE. 2011.
    [5] EC. Commission Regulation (EU) No 10/2011 of 14 January 2011 on Plastic Materials and Articles Intended to Come into Contact with Food.[EB/OL].[2021-1-24]. https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2011:012:0001:0089:EN:PDF
    [6] ALONSO-MAGDALENA P, QUESADA I, NADAL A. Endocrine disruptors in the etiology of type 2 diabetes mellitus[J]. Nat Rev Endocrinol, 2011, 7(6):346-353.
    [7] SAEIDNIA S, ABDOLLAHI M. Toxicological and pharmacological concerns on oxidative stress and related diseases[J]. Toxicol Appl Pharmacol, 2013, 273(3):442-455.
    [8] WHO. Diabetes[EB/OL].[2020-9-28] https://www.who.int/news-room/fact-sheets/detail/diabetes. 2020.
    [9] ALONSO-MAGDALENA P, MORIMOTO S, RIPOLL C, et al. The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance[J]. Environ Health Perspect, 2006, 114(1):106-112.
    [10] SORIANO S, ALONSO-MAGDALENA P, GARCÍA-ARÉVALO M, et al. Rapid insulinotropic action of low doses of bisphenol-A on mouse and human islets of Langerhans:Role of estrogen receptor β[J]. PLoS One, 2012, 7(2):e31109.
    [11] BANSAL A, RASHID C, XIN F, et al. Sex- and dose-specific effects of maternal bisphenol a exposure on pancreatic islets of first- and second-generation adult mice offspring[J]. Environ Health Perspect, 2017, 125(9):97022.
    [12] CHEN C, CHEN H, ZHANG Y, et al. TBtools:An integrative toolkit developed for interactive analyses of big biological data[J]. Mol Plant, 2020, 13(8):1194-1202.
    [13] HUANG D W, SHERMAN B T, LEMPICKI RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources[J]. Nat Protoc, 2009, 4(1):44-57.
    [14] HUANG D W, SHERMAN B T, LEMPICKI R A. Bioinformatics enrichment tools:Paths toward the comprehensive functional analysis of large gene lists[J]. Nucleic Acids Res, 2009, 37(1):1-13.
    [15] MARTINEZ-PINNA J, MARROQUI L, HMADCHA A, et al. Oestrogen receptor β mediates the actions of bisphenol-A on ion channel expression in mouse pancreatic beta cells[J]. Diabetologia, 2019, 62(9):1667-1680.
    [16] GARCÍA-ARÉVALO M, ALONSO-MAGDALENA P, SERVITJA JM, et al. Maternal exposure to bisphenol:A during pregnancy increases pancreatic β-cell growth during early life in male mice offspring[J]. Endocrinology, 2016, 157(11):4158-4171.
    [17] TAKAHASHI O, OISHI S. Disposition of orally administered 2,2-Bis(4-hydroxyphenyl)propane (bisphenol A) in pregnant rats and the placental transfer to fetuses[J]. Environ Health Perspect, 2000, 108(10):931-935.
    [18] ZALKO D, SOTO A M, DOLO L, et al. Biotransformations of bisphenol A in a mammalian model:Answers and new questions raised by low-dose metabolic fate studies in pregnant CD1 mice[J]. Environ Health Perspect, 2003, 111(3):309-319.
    [19] ALONSO-MAGDALENA P, VIEIRA E, SORIANO S, et al. Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring[J]. Environ Health Perspect, 2010, 118(9):1243-1250.
    [20] 史琳娜, 王柯, 邓玉娣,等. 脂噬对脂质代谢的调节作用及其分子机制[J]. 南方医科大学学报, 2019, 39(7):867-874.

    SHI L N, WANG K, DENG Y D, et al. Role of lipophagy in the regulation of lipid metabolism and the molecular mechanism[J]. Journal of Southern Medical University, 2019, 39(7):867-874(in Chinese).

    [21] BEM D, YOSHIMURA S, NUNES-BASTOS R, et al. Loss-of-function mutations in RAB18 cause Warburg micro syndrome[J]. Am J Hum Genet, 2011, 88(4):499-507.
    [22] KALININA T, GVNGÖR C, THIELTGES S, et al. Establishment and characterization of a new human pancreatic adenocarcinoma cell line with high metastatic potential to the lung[J]. BMC Cancer, 2010, 10:295.
    [23] HEDMAN A C, SMITH J M, SACKS D B. The biology of IQGAP proteins:beyond the cytoskeleton[J]. EMBO Rep, 2015, 16(4):427-446.
    [24] JIRTLE R L. Genomic imprinting and cancer[J]. Exp Cell Res, 1999, 248(1):18-24.
    [25] 龙健儿, 贺力强, 蔡霞. IGF-2r的结构和功能及其在胚胎发育中的作用[J]. 生命科学, 2005, 17(5):67-72.

    LONG J E, HE L Q,CAI X. IGF-2r structure, function and its role in the embryonic development[J]. Chinese Bulletin of Life Sciences, 2005, 17(5):67-72(in Chinese).

    [26] SAINI C, PETRENKO V, PULIMENO P, et al. A functional circadian clock is required for proper insulin secretion by human pancreatic islet cells[J]. Diabetes Obes Metab, 2016, 18(4):355-365.
    [27] LEI Z, JUNHUI L, PEIFENG L. Candidate genes mediated by estrogen-related receptor γ in pancreatic β cells[J]. J Biochem Mol Toxicol, 2019, 33(10):e22390.
    [28] GUPTA S C, HEVIA D, PATCHVA S, et al. Upsides and downsides of reactive oxygen species for cancer:The roles of reactive oxygen species in tumorigenesis, prevention, and therapy[J]. Antioxid Redox Signal, 2012, 16(11):1295-1322.
    [29] LI H S, ZHANG J Y, THOMPSON B S, et al. Rat mitochondrial ATP synthase ATP5G3:Cloning and upregulation in pancreas after chronic ethanol feeding[J]. Physiol Genomics, 2001, 6(2):91-98.
    [30] SHUBINA M Y, MUSINOVA Y R, SHEVAL E V. Proliferation, cancer, and aging-novel functions of the nucleolar methyltransferase fibrillarin?[J]. Cell Biol Int, 2018, 42(11):1463-1466.
    [31] MAHLAMÄKI E H, KAURANIEMI P, MONNI O, et al. High-resolution genomic and expression profiling reveals 105 putative amplification target genes in pancreatic cancer[J]. Neoplasia, 2004, 6(5):432-439.
    [32] CHEN B, JIAO Y, YAOLONG F, et al. The POLR2E rs3787016 polymorphism is strongly associated with the risk of female breast and cervical cancer[J]. Pathol Res Pract, 2019, 215(5):1061-1065.
    [33] ANTONACOPOULOU A G, GRIVAS P D, SKARLAS L, et al. POLR2F, ATP6V0A1 and PRNP expression in colorectal cancer:New molecules with prognostic significance?[J]. Anticancer Res, 2008, 28(2b):1221-1227.
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  • 收稿日期:  2020-10-13

BPA暴露对本体和子代胰岛β细胞转录组差异对比分析

    通讯作者: 白剑英, E-mail: jybai66@sxmu.edu.cn
  • 1. 山西医科大学公共卫生学院环境卫生教研室, 太原, 030001;
  • 2. 山西大学环境与资源学院环境健康研究中心, 太原, 030006
  • 收稿日期:  2020-10-13
基金项目:

国家自然科学基金（21906099），山西省教育厅高校科技创新项目（2020L0174，2020L0025）和山西省自然科学基金（201701D121140）资助.

摘要: 双酚A （BPA）作为一种典型的环境内分泌干扰物，与二型糖尿病和肥胖症等代谢类疾病密切相关.在这项研究中，旨在探讨BPA直接暴露以及围产期暴露对本体和子代胰岛β细胞影响的差异，从而实现对不同易感人群的精准预防与治疗.通过对GEO数据库中GSE126297和GSE82175两个数据集进行分析，共筛选出108个共有的差异基因，其中28个表达趋势一致，而另外80个表达趋势相反.随后对本体和子代单独的差异基因，以及共有差异基因进行了GO和KEGG对比分析.此外，利用String数据库和Cytoscape分析PPI网络中的紧密联系的基因，并将其可视化，进一步从28个表达趋势一致的基因中筛选出相互作用最为紧密的基因集1（Iqgap2，Igf2r和Rab18）；从80个表达趋势相反的基因中筛选出相互作用紧密的基因集2（Polr2f，Ccnt2，Polr2e，Kdm7a，Fbl）和基因集3（Atp5g2，Atp5o和Ndufa6）.最后，通过GEPIA在线验证上述基因在胰腺癌样本中的表达，研究发现Rab18，Polr2f，Polr2e，Fbl，Atp5g2，Atp5o和Ndufa6在胰腺癌病例中的表达均显著上升.同时，上述基因在本体中呈现显著上升趋势，而对于子代，只有Rab18显著上升，其他基因则呈下降趋势.综上，BPA对本体和子代的影响有一定的关联，其中关联的关键基因的异常表达可能会增加本体罹患胰腺癌的风险，而对于子代则会影响代谢过程和细胞结构.

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