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首页> 外文期刊>Environmental research >Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo
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Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo

机译:体外大鼠肝脏在体外肝脏肝脏肝单位和高剂量的双酚A诱导的转录组变化综合分析

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摘要

Bisphenol A (BPA), a synthetic monomer commonly included in the daily products, has a structure similar to the estrogen receptor agonist. Therefore BPA has been anticipated to interfere with the hormone metabolisms and cause diverse pathological conditions. But the effects of BPA on the genetic landscapes of liver or hepatic cells have not been fully established. Gene expressional changes induced by low- or high-dose of BPA were evaluated in 3D cultured human hepatoma cells (HepG2 spheroids) in vitro at 0, 0.5, 5 and 200 mu M and liver of rats exposed to BPA at 0, 0.5 and 250 mg/kg for 90 days in vivo. Functional enrichment analysis, pathway activity measurement and network analysis were performed using BPA-responsive genes. Treatment with BPA changed a lot of gene expressions in both HepG2 spheroids and rat livers depending on doses of BPA. Functional enrichment and pathway analysis show that lipid or steroid metabolism-related functions were altered by BPA in both HepG2 spheroids and livers of rats. Lipid metabolism-related functions altered by BPA formed a large cluster encompassing lipid biosynthesis, steroid metabolic process and cholesterol regulation process. It was also observed that distribution of pathway activities was correlated between HepG2 spheroids and rat livers at low-dose of BPA. Distance distribution in protein-protein interaction network also evidenced the closeness of BPA-responsive genes to metabolism pathways which include lipid metabolism. Collectively, we demonstrated that BPA greatly influenced overall gene expression and biological functions in both human hepatoma spheroids and rat liver, in which lipid- or steroid metabolism-associated genes were significantly altered by the exposure to BPA.
机译:双酚A(BPA),一种常用于日常产品中的合成单体,具有与雌激素受体激动剂类似的结构。因此,预计BPA将干扰激素代谢并导致不同的病理条件。但BPA对肝脏或肝细胞遗传景观的影响尚未得到完全建立。在0,0.5,5和200μm的3D培养的人肝癌细胞(HepG2球体)中,在3D培养的人肝癌细胞(HepG2球体)和0,0.5和250处暴露于BPA的大鼠肝脏,在3D培养的人肝癌细胞(HepG2球体)中进行基因表达变化。 Mg / kg体内90天。使用BPA响应基因进行功能性富集分析,途径活性测量和网络分析。用BPA治疗根据BPA的剂量而改变了两种HepG2球状体和大鼠肝脏中的大量基因表达。功能性富集和途径分析表明,在HEPG2球体和大鼠肝脏中BPA改变了脂质或类固醇相关功能。 BPA改变的脂质代谢相关功能形成了包含脂质生物合成,类固醇代谢过程和胆固醇调节过程的大型簇。还观察到,途径活性分布在低剂量BPA的HepG2球状体和大鼠肝脏之间存在相关性。蛋白质 - 蛋白质相互作用网络中的距离分布也显着地证明了BPA响应基因对代谢途径的密切,其包括脂质代谢。总的来说,我们证明BPA在人肝癌球状体和大鼠肝脏中大大影响了整体基因表达和生物学功能,其中通过暴露于BPA显着改变脂质或类固醇代谢相关基因。

著录项

  • 来源
    《Environmental research》 |2019年第6期|124-134|共11页
  • 作者单位

    Korea Inst Oriental Med Herbal Med Res Div Daejeon 34054 South Korea;

    Ewha Womans Univ Grad Sch Pharmaceut Sci Seoul 03760 South Korea;

    Korea Inst Toxicol Dev & Reprod Toxicol Res Grp Daejeon 34114 South Korea;

    Yonsei Univ Dept Epidemiol & Hlth Promot Grad Sch Publ Hlth Seoul 03722 South Korea|Yonsei Univ Inst Hlth Promot Grad Sch Publ Hlth Seoul 03722 South Korea;

    GENECAST Co Seoul 05838 South Korea;

    GENECAST Co Seoul 05838 South Korea;

    Korea Inst Oriental Med Herbal Med Res Div Daejeon 34054 South Korea;

    Ewha Womans Univ Grad Sch Pharmaceut Sci Seoul 03760 South Korea;

    Ewha Womans Univ Grad Sch Pharmaceut Sci Seoul 03760 South Korea;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Bisphenol A; Transcriptomics; Lipid metabolism; Hepatocyte spheroid; Rat;

    机译:双酚A;转录组织;脂质代谢;肝细胞球状;老鼠;

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