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文献 / Documents(1) |
公開日 |
2024-10-16 |
アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
出版社版DOI |
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関連識別子 |
https://doi.org/10.1371/journal.pone.0022976 |
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関連名称 |
10.1371/journal.pone.0022976 |
出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
タイトル |
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タイトル |
Paradoxical Regulation of Human FGF21 by Both Fasting and Feeding Signals : Is FGF21 a Nutritional Adaptation Factor? |
タイトル別表記 |
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その他のタイトル |
Paradoxical Regulation of Human FGF21 |
著者 |
上番増, 喬
竹谷, 豊
山本, 浩範
Amo, Kikuko
大南, 博和
Arai, Hidekazu
Takei, Yuichiro
増田, 真志
谷村, 綾子
原田, 永勝
(山中)奥村, 仙示
武田, 英二
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抄録 |
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内容記述 |
Fibroblast growth factor 21 (FGF21) has recently emerged as a metabolic hormone involved in regulating glucose and lipid metabolism in mouse, but the regulatory mechanisms and actions of FGF21 in humans remain unclear. Here we have investigated the regulatory mechanisms of the human FGF21 gene at the transcriptional level. A deletion study of the human FGF21 promoter (−1672 to +230 bp) revealed two fasting signals, including peroxisome proliferator-activated receptor α (PPARα) and glucagon signals, that independently induced human FGF21 gene transcription in mouse primary hepatocytes. In addition, two feeding signals, glucose and xylitol, also dose-dependently induced human FGF21 gene transcription and mRNA expression in both human HepG2 cells and mouse primary hepatocytes. FGF21 protein expression and secretion were also induced by high glucose stimulation. The human FGF21 promoter (−1672 to +230 bp) was found to have a carbohydrate-responsive element at −380 to −366 bp, which is distinct from the PPAR response element (PPRE). Knock-down of the carbohydrate response element binding protein by RNAi diminished glucose-induced human FGF21 transcription. Moreover, we found that a region from −555 to −443 bp of the human FGF21 promoter region exerts an important role in the activation of basic transcription. In conclusion, human FGF21 gene expression is paradoxically and independently regulated by both fasting and feeding signals. These regulatory mechanisms suggest that human FGF21 is increased with nutritional crisis, including starvation and overfeeding. |
書誌情報 |
en : PLOS ONE
巻 6,
号 8,
p. e22976,
発行日 2011-08-01
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収録物ID |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
19326203 |
出版者 |
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出版者 |
PLOS |
権利情報 |
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権利情報 |
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
EID |
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識別子 |
241404 |
言語 |
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言語 |
eng |