...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >The Role of Long Noncoding RNA H19 in Gender Disparity of Cholestatic Liver Injury in Multidrug Resistance 2 Gene Knockout Mice
【24h】

The Role of Long Noncoding RNA H19 in Gender Disparity of Cholestatic Liver Injury in Multidrug Resistance 2 Gene Knockout Mice

机译：长非分量RNA H19在多药抗性2基因敲除小鼠中胆固性肝损伤性别差异的作用

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The multidrug resistance 2 knockout (Mdr2(-/-)) mouse is a well-established model of cholestatic cholangiopathies. Female Mdr2(-/-) mice develop more severe hepatobiliary damage than male Mdr2(-/-) mice, which is correlated with a higher proportion of taurocholate in the bile. Although estrogen has been identified as an important player in intrahepatic cholestasis, the underlying molecular mechanisms of gender-based disparity of cholestatic injury remain unclear. The long noncoding RNA H19 is an imprinted, maternally expressed, and estrogen-targeted gene, which is significantly induced in human fibrotic/cirrhotic liver and bile duct-ligated mouse liver. However, whether aberrant expression of H19 accounts for gender-based disparity of cholestatic injury in Mdr2(-/-) mice remains unknown. The current study demonstrated that H19 was markedly induced (similar to 200-fold) in the livers of female Mdr2(-/-) mice at advanced stages of cholestasis (100 days old) but not in age-matched male Mdr2(-/-) mice. During the early stages of cholestasis, H19 expression was minimal. We further determined that hepatic H19 was mainly expressed in cholangiocytes, not hepatocytes. Both taurocholate and estrogen significantly activated the extracellular signal-regulated kinase 1/2 signaling pathway and induced H19 expression in cholangiocytes. Knocking down H19 not only significantly reduced taurocholate/estrogen-induced expression of fibrotic genes and sphingosine 1-phosphate receptor 2 in cholangiocytes but also markedly reduced cholestatic injury in female Mdr2(-/-) mice. Furthermore, expression of small heterodimer partner was substantially inhibited at advanced stages of liver fibrosis, which was reversed by H19 short hairpin RNA in female Mdr2(-/-) mice. Similar findings were obtained in human primary sclerosing cholangitis liver samples. Conclusion: H19 plays a critical role in the disease progression of cholestasis and represents a key factor that causes the gender disparity of cholestatic liver injury in Mdr2(-/-) mice.
机译：多药电阻2敲除（MDR2（ - / - ））小鼠是富于胆管胆管素的良好模型。雌性MDR2（ - / - ）小鼠比男性MDR2（ - / - ）小鼠产生更严重的肝胆损伤，其与胆汁中的牛磺比比例较高。虽然雌激素已被鉴定为肝内胆汁淤积症的重要球员，但胆汁损伤的性别差异的基于性别差异的潜在分子机制仍不清楚。长度非致rna h19是印迹，母体表达和雌激素靶向基因，其在人纤维化/肝硬化肝脏和胆管连接的小鼠肝脏中显着诱导。然而，H19的异常表达是否占MDR2（ - / - ）小鼠中的基于性别胆汁损伤的基于性损伤的差异仍然未知。目前的研究表明，H19在胆汁淤积（100天大）的高级阶段的女性MDR2（ - / - ）小鼠中明显诱导（类似于200倍），但不在年龄匹配的男性MDR2（ - / - ） 老鼠。在胆汁淤积的早期阶段，H19表达最小。我们进一步确定肝脏H19主要用胆管细胞，而不是肝细胞表达。牛磺酸酯和雌激素均显着激活细胞外信号调节激酶1/2信号通路，并在胆管细胞中诱导H19表达。敲击H19不仅显着降低了胆管细胞的纤维化基因和鞘氨醇1-磷酸受体2的纤维化基因和鞘氨酸1-磷酸受体2的表达，而且显着降低了雌性MDR2（ - / - ）小鼠的胆汁淤积损伤。此外，在肝纤维化的先进阶段，小异二聚体配偶体的表达显着抑制了雌性MDR2（ - / - ）小鼠的H19短发夹RNA逆转。在人原发性硬化胆管炎肝脏样品中获得了类似的发现。结论：H19在胆汁淤积疾病进展中起着关键作用，代表了在MDR2（/ - / - ）小鼠中引起胆汁肝损伤的性别差异的关键因素。

著录项

  • 来源
  • 作者

    Li Xiaojiaoyang; Liu Runping; Yang Jing; Sun Lixin; Zhang Luyong; Jiang Zhenzhou; Puri Puneet; Gurley Emily C.; Lai Guanhua; Tang Yuping; Huang Zhiming; Pandak William M.; Hylemon Phillip B.; Zhou Huiping;

  • 作者单位

    China Pharmaceut Univ Jiangsu Key Lab Drug Screening Nanjing Jiangsu Peoples R China;

    Virginia Commonwealth Univ Dept Microbiol &

    Immunol Richmond VA 23298 USA;

    China Pharmaceut Univ Jiangsu Key Lab Drug Screening Nanjing Jiangsu Peoples R China;

    China Pharmaceut Univ Jiangsu Key Lab Drug Screening Nanjing Jiangsu Peoples R China;

    China Pharmaceut Univ Jiangsu Key Lab Drug Screening Nanjing Jiangsu Peoples R China;

    China Pharmaceut Univ Jiangsu Key Lab Drug Screening Nanjing Jiangsu Peoples R China;

    Virginia Commonwealth Univ Dept Internal Med Div Gastroenterol Hepatol &

    Nutr Richmond VA USA;

    Virginia Commonwealth Univ Dept Microbiol &

    Immunol Richmond VA 23298 USA;

    Virginia Commonwealth Univ Dept Pathol Med Coll Virginia Campus Richmond VA USA;

    Nanjing Univ Chinese Med Jiangsu Collaborat Innovat Ctr Chinese Med Resour Nanjing Jiangsu;

    Wenzhou Med Univ Affiliated Hosp 1 Dept Gastroenterol Wenzhou Peoples R China;

    Virginia Commonwealth Univ Dept Microbiol &

    Immunol Richmond VA 23298 USA;

    Virginia Commonwealth Univ Dept Microbiol &

    Immunol Richmond VA 23298 USA;

    Virginia Commonwealth Univ Dept Microbiol &

    Immunol Richmond VA 23298 USA;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 消化系及腹部疾病;
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号