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Thyroid hormone-responsive SPOT 14 homolog promotes hepatic lipogenesis, and its expression is regulated by Liver X receptor through a sterol regulatory element-binding protein 1c-dependent mechanism in mice
Wu, Jing1,4; Wang, Chunjiong1; Li, Shuo1; Li, Sha1; Wang, Wanyi1; Li, Jing1; Chi, Yujing1; Yang, Hang1; Kong, Xiaomu1; Zhou, Yunfeng1; Dong, Chengyan5; Wang, Fan5; Xu, Guoheng1; Yang, Jichun1; Gustafsson, Jan-Ake2,3; Guan, Youfei1
刊名HEPATOLOGY
2013-08-01
DOI10.1002/hep.26272
58期:2页:617-628
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Gastroenterology & Hepatology
研究领域[WOS]Gastroenterology & Hepatology
关键词[WOS]FATTY LIVER ; LXR-ALPHA ; NUCLEAR RECEPTORS ; HUMAN HEPATOCYTES ; GENE-EXPRESSION ; DEFICIENT MICE ; KNOCKOUT MICE ; METABOLISM ; DISEASE ; BETA
英文摘要

The protein, thyroid hormone-responsive SPOT 14 homolog (Thrsp), has been reported to be a lipogenic gene in cultured hepatocytes, implicating an important role of Thrsp in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Thrsp expression is known to be regulated by a variety of transcription factors, including thyroid hormone receptor, pregnane X receptor, and constitutive androstane receptor. Emerging in vitro evidence also points to a critical role of liver X receptor (LXR) in regulating Thrsp transcription in hepatocytes. In the present study, we showed that Thrsp was up-regulated in livers of db/db mice and high-fat-diet-fed mice, two models of murine NAFLD. Hepatic overexpression of Thrsp increased triglyceride accumulation with enhanced lipogenesis in livers of C57Bl/6 mice, whereas hepatic Thrsp gene silencing attenuated the fatty liver phenotype in db/db mice. LXR activator TO901317 induced Thrsp expression in livers of wild-type (WT) and LXR- gene-deficient mice, but not in LXR- or LXR-/ double-knockout mice. TO901317 treatment significantly enhanced hepatic sterol regulatory element-binding protein 1c (SREBP-1c) expression and activity in WT mice, but failed to induce Thrsp expression in SREBP-1c gene-deficient mice. Sequence analysis revealed four LXR response-element-like elements and one sterol regulatory element (SRE)-binding site within a -2,468 approximate to+1-base-pair region of the Thrsp promoter. TO901317 treatment and LXR- overexpression failed to induce, whereas overexpression of SREBP-1c significantly increased Thrsp promoter activity. Moreover, deletion of the SRE site completely abolished SREBP-1c-induced Thrsp transcription. Conclusion: Thrsp is a lipogenic gene in the liver that is induced by the LXR agonist through an LXR--mediated, SREBP-1c-dependent mechanism. Therefore, Thrsp may represent a potential therapeutic target for the treatment of NAFLD. (Hepatology 2013;58:617-628)

语种英语
WOS记录号WOS:000322996400021
项目编号2012CB517504/2011ZX09102 ; 2009CB941603 ; 2010CB912503 ; 2011CB707703 ; 2013CB733802 ; 30870905/81030003 ; 30900499 ; 20090001120042
资助机构Ministry of Science and Technology ; Natural Science Foundation ; National Natural Science Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education ; Swedish Research Council ; Robert A. Welch Foundation
引用统计
被引频次:24[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59346
专题北京大学医药卫生分析中心
北京大学基础医学院
北京大学第一临床医学院_医学影像科
北京大学第二临床医学院_中心实验室
北京大学第三临床医学院_心脏外科
作者单位1.Peking Univ, Dept Physiol & Pathophysiol, Hlth Sci Ctr, Key Lab Cardiovasc Sci,Minist Educ, Beijing 1000191, Peoples R China
2.Univ Houston, Ctr Nucl Receptors & Cell Signaling, Houston, TX 77204 USA
3.Karolinska Inst, Novum, Dept BioSci & Nutr, Huddinge, Sweden
4.Hebei United Univ, Dept Pathophysiol, Tangshan, Peoples R China
5.Peking Univ, Med Isotopes Res Ctr, Hlth Sci Ctr, Beijing 1000191, Peoples R China
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GB/T 7714
Wu, Jing,Wang, Chunjiong,Li, Shuo,et al. Thyroid hormone-responsive SPOT 14 homolog promotes hepatic lipogenesis, and its expression is regulated by Liver X receptor through a sterol regulatory element-binding protein 1c-dependent mechanism in mice[J]. HEPATOLOGY,2013,58(2):617-628.
APA Wu, Jing.,Wang, Chunjiong.,Li, Shuo.,Li, Sha.,Wang, Wanyi.,...&Guan, Youfei.(2013).Thyroid hormone-responsive SPOT 14 homolog promotes hepatic lipogenesis, and its expression is regulated by Liver X receptor through a sterol regulatory element-binding protein 1c-dependent mechanism in mice.HEPATOLOGY,58(2),617-628.
MLA Wu, Jing,et al."Thyroid hormone-responsive SPOT 14 homolog promotes hepatic lipogenesis, and its expression is regulated by Liver X receptor through a sterol regulatory element-binding protein 1c-dependent mechanism in mice".HEPATOLOGY 58.2(2013):617-628.
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