FAM3A is a target gene of peroxisome proliferator-activated receptor gamma.
FAM3A is a target gene of peroxisome proliferator-activated receptor gamma.
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FAM3A 是过氧化物酶体增殖物激活受体 γ 的靶基因。
DOI：
10.1016/j.bbagen.2013.03.029
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发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Yang, Jichun
中科院分区：
文献类型：
--
作者：
Li, Jing;Xu, Guoheng;Guan, Youfei;Yang, Jichun
FAM3A是FAM3基因家族的第一个成员，迄今为止，其生物学功能尚不清楚。我们的目的是研究FAM3A在肝细胞中的表达是否受到过氧化物酶体增殖激活受体（PPARs）的调节。方法与结果采用荧光素酶报告基因检测系统检测人和小鼠FAM3A基因启动子的转录活性。PPARγ激动剂罗格列酮诱导原代培养小鼠肝细胞和人HepG2细胞中FAM3A的表达。PPARγ拮抗剂阻断罗格列酮诱导的FAM3A表达，而PPARγ过表达则刺激HepG2细胞中FAM3A的表达。相比之下，PPARα激动剂非诺贝特或PPARβ激动剂GW0742未能影响FAM3A在HepG2细胞中的表达。人类和小鼠FAM3A启动子的转录活性受PPARγ激活的显著刺激，但不受PPARα和PPARβ激活的影响。染色质免疫沉淀（ChIP）分析显示，PPARγ与位于人类FAM3A启动子- 1258/ - 1246的推定过氧化物酶体增殖反应元件（PPRE）直接结合。该ppre样基序的定点突变消除了PPARγ对人类FAM3A启动子转录活性的刺激作用。在体内，口服罗格列酮可上调C57BL/6小鼠和db/db小鼠肝脏中FAM3A的表达。此外，PPARγ活化对FAM3A的上调与肝细胞中磷酸化Akt （pAkt）水平升高相关。结论sfam3a是一种新的PPARγ靶基因。PPARγ活化对FAM3A的上调与肝细胞中pAkt水平升高相关。一般意义FAM3A的调节可能参与PPARγ在肝脏中的代谢作用。
BACKGROUNDTo 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 RESULTSThe transcriptional activity of human and mouse FAM3A gene promoters was determined by luciferase reporter assay system. PPARγ agonist rosiglitazone induced FAM3A expression in primary cultured mouse hepatocytes and human HepG2 cells. PPARγ antagonism blocked rosiglitazone-induced FAM3A expression, whereas PPARγ overexpression stimulated FAM3A expression in HepG2 cells. In contrast, PPARα agonist fenofibrate or PPARβ agonist GW0742 failed to affect FAM3A expression in HepG2 cells. The transcriptional activities of human and mouse FAM3A promoters were markedly stimulated by PPARγ activation, but not by PPARα and PPARβ activation. Chromatin immunoprecipitation (ChIP) assay revealed a direct binding of PPARγ 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 PPARγ'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 PPARγ activation was correlated with increased level of phosphorylated Akt (pAkt) in liver cells.CONCLUSIONSFAM3A as a novel target gene of PPARγ. Upregulation of FAM3A by PPARγ activation is correlated with increased pAkt level in liver cells.GENERAL SIGNIFICANCEUpregulation of FAM3A might contribute to PPARγ's metabolic effects in the liver.
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影响因子：
19.6
作者：
Hong Zhang;Yuan-yuan Li;Yanbo Fan;Jing Wu;Beilei Zhao;Y. Guan;S. Chien;Nanping Wang
通讯作者：
Hong Zhang;Yuan-yuan Li;Yanbo Fan;Jing Wu;Beilei Zhao;Y. Guan;S. Chien;Nanping Wang
DOI：
10.1016/j.bbaexp.2005.07.003
发表时间：
2005-09-25
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Burkhardt, BR;Yang, MC;Wolf, BA
通讯作者：
Wolf, BA
PANDER 与肝细胞膜结合并抑制 HepG2 细胞中的胰岛素信号传导。
影响因子：
3.5
作者：
Yang, Jichun;Wang, Chunjiong;Wolf, Bryan A.
通讯作者：
Wolf, Bryan A.
影响因子：
24.5
作者：
Hearnshaw, Sarah A.;Logan, Richard F. A.;Palmer, Kelvin R.
通讯作者：
Palmer, Kelvin R.
影响因子：
3.5
作者：
Pilipenko, VV;Reece, A;Greinwald, JH
通讯作者：
Greinwald, JH