Orphan nuclear receptor ERRγ is a key regulator of human fibrinogen gene expression
Fibrinogen, 1 of 13 coagulation factors responsible for normal blood clotting, is synthesized by hepatocytes. Detailed roles of the orphan nuclear receptors regulating fibrinogen gene expression have not yet been fully elucidated. Here, we identified estrogen-related receptor gamma (ERRγ) as a novel...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
July 27, 2017
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| In: |
PLOS ONE
Year: 2017, Volume: 12, Issue: 7 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0182141 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1371/journal.pone.0182141 Verlag, kostenfrei, Volltext: http://journals.plos.org.ezproxy.medma.uni-heidelberg.de/plosone/article?id=10.1371/journal.pone.0182141 
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| Author Notes: | Yaochen Zhang, Don-Kyu Kim, Yan Lu, Yoon Seok Jung, Ji-min Lee, Young-Hoon Kim, Yong Soo Lee, Jina Kim, Bedair Dewidar, Won-IL Jeong, In-Kyu Lee, Sung Jin Cho, Steven Dooley, Chul-Ho Lee, Xiaoying Li, Hueng-Sik Choi |
| Summary: | Fibrinogen, 1 of 13 coagulation factors responsible for normal blood clotting, is synthesized by hepatocytes. Detailed roles of the orphan nuclear receptors regulating fibrinogen gene expression have not yet been fully elucidated. Here, we identified estrogen-related receptor gamma (ERRγ) as a novel transcriptional regulator of human fibrinogen gene expression. Overexpression of ERRγ specially increased fibrinogen expression in human hepatoma cell line. Cannabinoid receptor types 1(CB1R) agonist arachidonyl-2'-chloroethylamide (ACEA) up-regulated transcription of fibrinogen via induction of ERRγ, whereas knockdown of ERRγ attenuated fibrinogen expression. Deletion analyses of the fibrinogen γ (FGG) gene promoter and ChIP assays revealed binding sites of ERRγ on human fibrinogen γ gene promoter. Moreover, overexpression of ERRγ was sufficient to increase fibrinogen gene expression, whereas treatment with GSK5182, a selective inverse agonist of ERRγ led to its attenuation in cell culture. Finally, fibrinogen and ERRγ gene expression were elevated in liver tissue of obese patients suggesting a conservation of this mechanism. Overall, this study elucidates a molecular mechanism linking CB1R signaling, ERRγ expression and fibrinogen gene transcription. GSK5182 may have therapeutic potential to treat hyperfibrinogenemia. |
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| Item Description: | Gesehen am 14.06.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0182141 |