中国科学技术大学学报 ›› 2010, Vol. 40 ›› Issue (7): 673-678.DOI: 10.3969/j.issn.0253-2778.2010.07.003

• 原创论文 • 上一篇    下一篇

饥饿状态下HNF4α对MTP的表达调控

瞿林兵   

  1. 1.中国科学院广州生物医药与健康研究院,广东广州 510530; 2.中国科学技术大学生命科学学院,安徽合肥 230027
  • 收稿日期:2010-03-24 修回日期:2010-05-23 出版日期:2010-07-31 发布日期:2010-07-31
  • 通讯作者: 陈凌
  • 作者简介:瞿林兵,男,1982年生,学士. 研究方向: 磷脂酶A2基因敲除小鼠表型研究. E-mail: qulinbin@mail.ustc.edu.cn
  • 基金资助:
    国家重点基础研究发展(973)计划(2006CB50390)和中国科学院知识创新计划(KSCX2-YW-R-085)资助.

Starvation induced MTP expression in part through HNF4α

QU Linbing   

  1. 1.Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; 2.School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
  • Received:2010-03-24 Revised:2010-05-23 Online:2010-07-31 Published:2010-07-31

摘要: 肝细胞核因子4α(HNF4α)是肝脏中一种重要的转录因子,其参与多个代谢途径的调控.微粒体甘油三酯转运蛋白(MTP)是极低密度脂蛋白装配和分泌过程的限速酶.C57BL/6J小鼠中研究发现,饥饿可以诱导肝细胞MTP基因的表达.在HepG2细胞中进一步证实饥饿可以诱导MTP表达,同时HNF4α表达也显著上升.实验证实MTP是HNF4α的靶基因之一,用腺病毒介导的HNF4α过表达和HNF4α的激动剂均显著提高MTP的表达;HNF4α特异性siRNA抑制HNF4α的表达,MTP的mRNA和蛋白水平相应下调.结果证明,在饥饿状态下可以诱导MTP 和HNF4α的表达,MTP的表达量上升是受到HNF4α的转录调控.

关键词: 肝细胞核因子4α, 微粒体甘油三酯转运蛋白, 饥饿

Abstract: Hepatocyte nuclear factor 4α (HNF4α) is an important transcription factor governing the expression of genes involved in multiple metabolic pathways. Microsomal triglyceride transfer protein (MTP) is a rate-limiting enzyme played a role in the assembly and secretion of very low density lipoproteins (VLDLs). Fasting induces MTP expression in C57BL/6J mice. In HepG2 cells, we further demonstrate that starvation induces MTP expression, meanwhile enhances HNF4α mRNA level. It was found that MTP is an HNF4α target gene. Moreover, adenovirus mediated HNF4α overexpression and HNF4α agonists induce MTP expression in HepG2 cells. HNF4α specific siRNA represses HNF4α and MTP expression. These results suggest that starvation induces MTP expression in part through HNF4α.

Key words: Hepatocyte nuclear factor 4α, microsomal triglyceride transfer protein, starvation