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论文题目: MicroRNA-214 Suppresses Gluconeogenesis by Targeting Activating Transcriptional Factor 4
英文论文题目: MicroRNA-214 Suppresses Gluconeogenesis by Targeting Activating Transcriptional Factor 4
第一作者: Li, K; Zhang, J; Yu, JJ; Liu, B; Guo, YJ; Deng, JL; Chen, SH; Wang, CX; Guo, FF
英文第一作者: Li, K; Zhang, J; Yu, JJ; Liu, B; Guo, YJ; Deng, JL; Chen, SH; Wang, CX; Guo, FF
联系作者: Guo, FF (reprint author), Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Guo, FF (reprint author), Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
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发表年度: 2015
卷: 290
期: 13
页码: 8185-8195
摘要: Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of microRNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinase A signaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat diet-induced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1(FOXO1) transcriptional activity. Finally, liver-specific miR214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis.
英文摘要: Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of microRNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinase A signaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat diet-induced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1(FOXO1) transcriptional activity. Finally, liver-specific miR214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis.
刊物名称: JOURNAL OF BIOLOGICAL CHEMISTRY
英文刊物名称: JOURNAL OF BIOLOGICAL CHEMISTRY
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学科: Biochemistry & Molecular Biology
英文学科: Biochemistry & Molecular Biology
影响因子: 4.573
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论文类别: Article
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