• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Human Glucocorticoid Receptor β Regulates Gluconeogenesis and Inflammation in Mouse Liver
【24h】

Human Glucocorticoid Receptor β Regulates Gluconeogenesis and Inflammation in Mouse Liver

机译：人糖皮质激素受体β调节小鼠肝脏的糖异生和炎症

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

While in vitro studies have demonstrated that a glucocorticoid receptor (GR) splice isoform, β-isoform of human GR (hGRβ), acts as a dominant-negative inhibitor of the classic hGRα and confers glucocorticoid resistance, the in vivo function of hGRβ is poorly understood. To this end, we created an adeno-associated virus (AAV) to express hGRβ in the mouse liver under the control of the hepatocyte-specific promoter. Genome-wide expression analysis of mouse livers showed that hGRβ significantly increased the expression of numerous genes, many of which are involved in endocrine system disorders and the inflammatory response. Physiologically, hGRβ antagonized GRα's function and attenuated hepatic gluconeogenesis through downregulation of phosphoenolpyruvate carboxykinase (PEPCK) in wild-type (WT) mouse liver. Interestingly, however, hGRβ did not repress PEPCK in GR liver knockout (GRLKO) mice. In contrast, hGRβ regulates the expression of STAT1 in the livers of both WT and GRLKO mice. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays demonstrated that hGRβ binds to the intergenic glucocorticoid response element (GRE) of the STAT1 gene. Furthermore, treatment with RU486 inhibited the upregulation of STAT1 mediated by hGRβ. Finally, our array data demonstrate that hGRβ regulates unique components of liver gene expression in vivo by both GRα-dependent and GRα-independent mechanisms.
机译：尽管体外研究表明，糖皮质激素受体（GR）剪接异构体，即人类GR（hGRβ）的β-异构体，可作为经典hGRα的显性负抑制剂，赋予糖皮质激素抗性，对hGRβ的体内功能了解甚少。为此，我们创建了一种腺相关病毒（AAV）在肝细胞特异性启动子的控制下在小鼠肝脏中表达hGRβ。小鼠肝脏的全基因组表达分析表明，hGRβ显着增加了许多基因的表达，其中许多基因与内分泌系统疾病和炎症反应有关。在生理上，hGRβ通过下调野生型（WT）小鼠肝脏中的磷酸烯醇丙酮酸羧化激酶（PEPCK）来拮抗GRα的功能并减弱肝糖异生。然而，有趣的是，hGRβ不能抑制GR肝敲除（GRLKO）小鼠的PEPCK。相反，hGRβ调节WT和GRLKO小鼠肝脏中STAT1的表达。染色质免疫沉淀（ChIP）和荧光素酶报告基因检测证明hGRβ与STAT1基因的基因间糖皮质激素反应元件（GRE）结合。此外，用RU486治疗抑制了hGRβ介导的STAT1的上调。最后，我们的阵列数据表明，hGRβ通过GRα依赖性和GRα依赖性机制调节体内肝脏基因表达的独特成分。

著录项

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