Activation of farnesoid X receptor induces RECK expression in mouse liver
Activation of farnesoid X receptor induces RECK expression in mouse liver
复制标题
法尼醇X受体激活诱导小鼠肝脏RECK表达
DOI：
10.1016/j.bbrc.2013.11.082
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发表时间：
2014-01-03
影响因子：
3.1
通讯作者：
Gu, Jianxin
中科院分区：
文献类型：
--
作者：
Peng, Xiaomin;Wu, Weibin;Gu, Jianxin
法尼醇X受体(FXR)属于配体激活的核受体超家族，是一种转录因子，调节胆汁酸稳态、脂蛋白和糖代谢等多种基因的转录。在本研究中，我们发现基质金属蛋白酶的膜锚定抑制因子RECK是FXR在小鼠肝脏中的一个新的靶基因。我们发现，FXR激动剂在体内和体外都显著增强了肝脏RECK的mRNA和蛋白表达。FXR通过与位于小鼠RECK基因内含子1的FXR反应元件直接结合来调控RECK的转录。此外，FXR激动剂逆转了喂食蛋氨酸和胆碱缺乏饮食的小鼠肝脏中RECK的下调。综上所述，我们的数据表明RECK是FXR在小鼠肝脏中的一个新的转录靶点，为更好地了解FXR在肝脏中的功能提供了线索。(C)2013 Elsevier Inc.保留所有权利。
Farnesoid X receptor (FXR) belongs to the ligand-activated nuclear receptor superfamily, and functions as a transcription factor regulating the transcription of numerous genes involved in bile acid homeostasis, lipoprotein and glucose metabolism. In the present study, we identified RECK, a membrane-anchored inhibitor of matrix metalloproteinases, as a novel target gene of FXR in mouse liver. We found that FXR agonist substantially augmented hepatic RECK mRNA and protein expression in vivo and in vitro. FXR regulated the transcription of RECK through directly binding to FXR response element located within intron 1 of the mouse RECK gene. Moreover, FXR agonist reversed the down-regulation of RECK in the livers from mice fed a methionine and choline deficient diet. In summary, our data suggest that RECK is a novel transcriptional target of FXR in mouse liver, and provide clues to better understanding the function of FXR in liver. (C) 2013 Elsevier Inc. All rights reserved.