IR@PKUHSC  > 北京大学第二临床医学院
学科主题临床医学
FAM3A is a target gene of peroxisome proliferator-activated receptor gamma
Zhou, Yanlan; Jia, Shi; Wang, Chunjiong; Chen, Zhenzhen; Chi, Yujing1; Li, Jing2; Xu, Guoheng3,4; Guan, Youfei3,4; Yang, Jichun3,4
关键词FAM3A Nuclear receptor PPAR gamma PPRE Akt
刊名BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
2013-08-01
DOI10.1016/j.bbagen.2013.03.029
1830期:8页:4160-4170
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]PANCREATIC-DERIVED FACTOR ; FATTY LIVER IMPROVEMENT ; LEPTIN-DEFICIENT MICE ; PPAR-GAMMA ; FACTOR PANDER ; HEPATIC STEATOSIS ; BETA-CELLS ; NONALCOHOLIC STEATOHEPATITIS ; FASTING HYPERGLYCEMIA ; INSULIN-RESISTANCE
英文摘要

Background: To date, the biological function of FAM3A, the first member of FAM3 gene family, remains unknown. We aimed to investigate whether the expression of FAM3A in liver cells is regulated by peroxisome proliferator-activated receptors (PPARs).

Methods and results: The transcriptional activity of human and mouse FAM3A gene promoters was determined by luciferase reporter assay system. PPAR gamma agonist rosiglitazone induced FAM3A expression in primary cultured mouse hepatocytes and human HepG2 cells. PPAR gamma antagonism blocked rosiglitazone-induced FAM3A expression, whereas PPAR gamma overexpression stimulated FAM3A expression in HepG2 cells. In contrast PPAR alpha agonist fenofibrate or PPAR beta agonist GW0742 failed to affect FAM3A expression in HepG2 cells. The transcriptional activities of human and mouse FAM3A promoters were markedly stimulated by PPAR gamma activation, but not by PPAR alpha and PPAR beta activation. Chromatin immunoprecipitation (ChIP) assay revealed a direct binding of PPAR gamma to the putative peroxisome proliferator response element (PPRE) located at -1258/-1246 in the human FAM3A promoter. Site-directed mutagenesis of this PPRE-like motif abolished PPAR gamma′s stimulatory effect on the transcriptional activity of human FAM3A promoter. In vivo, oral rosiglitazone treatment upregulated FAM3A expression in the livers of C57BL/6 mice and db/db mice. Moreover, upregulation of FAM3A by PPAR gamma activation was correlated with increased level of phosphorylated Akt (pAkt) in liver cells.

Conclusions: FAM3A as a novel target gene of PPAR gamma. Upregulation of FAM3A by PPAR gamma activation is correlated with increased pAkt level in liver cells.

General significance: Upregulation of FAM3A might contribute to PPAR gamma′s metabolic effects in the liver. (c) 2013 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000320896100016
引用统计
被引频次:15[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/400002259/61494
专题北京大学第二临床医学院
北京大学基础医学院
北京大学第二临床医学院_中心实验室
作者单位1.Peking Univ Peoples Hosp, Ctr Lab, Beijing, Peoples R China
2.Peking Beijing Univ Diabet Ctr, Beijing, Peoples R China
3.Peking Univ Peoples Hosp, Dept Gastroenterol, Beijing, Peoples R China
4.Peking Beijing Univ Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
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Zhou, Yanlan,Jia, Shi,Wang, Chunjiong,et al. FAM3A is a target gene of peroxisome proliferator-activated receptor gamma[J]. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS,2013,1830(8):4160-4170.
APA Zhou, Yanlan.,Jia, Shi.,Wang, Chunjiong.,Chen, Zhenzhen.,Chi, Yujing.,...&Yang, Jichun.(2013).FAM3A is a target gene of peroxisome proliferator-activated receptor gamma.BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS,1830(8),4160-4170.
MLA Zhou, Yanlan,et al."FAM3A is a target gene of peroxisome proliferator-activated receptor gamma".BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS 1830.8(2013):4160-4170.
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