Activation of the nuclear receptor FXR induces fibrinogen expression: a new role for bile acid signaling
Three genes, fibrinogen-α (FBGα), -β, and -γ, encode proteins that make up the mature FBG protein complex. This complex is secreted from the liver and plays a key role in coagulation in response to vascular disruption. We identified all three FBG genes in a screen designed to isolate genes that are...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2005-03-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S002222752034030X |
| _version_ | 1818602513673224192 |
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| author | Andrew M. Anisfeld Heidi R. Kast-Woelbern Hans Lee Yanqiao Zhang Florence Y. Lee Peter A. Edwards |
| author_facet | Andrew M. Anisfeld Heidi R. Kast-Woelbern Hans Lee Yanqiao Zhang Florence Y. Lee Peter A. Edwards |
| author_sort | Andrew M. Anisfeld |
| collection | DOAJ |
| description | Three genes, fibrinogen-α (FBGα), -β, and -γ, encode proteins that make up the mature FBG protein complex. This complex is secreted from the liver and plays a key role in coagulation in response to vascular disruption. We identified all three FBG genes in a screen designed to isolate genes that are regulated by the farnesoid X receptor (FXR; NR1H4). Treatment of human hepatoma cells with either naturally occurring or synthetic [3-(2,6-dichlorophenyl)-4-(3′-carboxy-2-chloro-stilben-4-yl)-oxymethyl-5-isopropyl-isoxazole] FXR ligands resulted in the induction of transcripts for all three genes. The induction of FBGβ mRNA in response to activated FXR appears to be a primary transcriptional response, as it is blocked by actinomycin D but not by cycloheximide. Four FXR isoforms were recently identified that differ either at their N termini and/or by the presence of four amino acids in the hinge region. Interestingly, the activities of the human FBGβ promoter-reporter constructs were highly induced by FXR isoforms that lack the four amino acid insert.The observation that all three FBG subunits are induced by specific FXR isoforms, in response to FXR ligands, suggests that bile acids and FXR modulate fibrinolytic activity. |
| first_indexed | 2024-12-16T13:08:29Z |
| format | Article |
| id | doaj.art-d308df5bda65440aa920c9eb7d2440fe |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-16T13:08:29Z |
| publishDate | 2005-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-d308df5bda65440aa920c9eb7d2440fe2022-12-21T22:30:41ZengElsevierJournal of Lipid Research0022-22752005-03-01463458468Activation of the nuclear receptor FXR induces fibrinogen expression: a new role for bile acid signalingAndrew M. Anisfeld0Heidi R. Kast-Woelbern1Hans Lee2Yanqiao Zhang3Florence Y. Lee4Peter A. Edwards5Department of Biological Chemistry and Medicine, University of California Los Angeles, Los Angeles, CA 90095; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095Department of Biological Chemistry and Medicine, University of California Los Angeles, Los Angeles, CA 90095; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095Department of Biological Chemistry and Medicine, University of California Los Angeles, Los Angeles, CA 90095; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095Department of Biological Chemistry and Medicine, University of California Los Angeles, Los Angeles, CA 90095; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095Department of Biological Chemistry and Medicine, University of California Los Angeles, Los Angeles, CA 90095; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095Department of Biological Chemistry and Medicine, University of California Los Angeles, Los Angeles, CA 90095; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095Three genes, fibrinogen-α (FBGα), -β, and -γ, encode proteins that make up the mature FBG protein complex. This complex is secreted from the liver and plays a key role in coagulation in response to vascular disruption. We identified all three FBG genes in a screen designed to isolate genes that are regulated by the farnesoid X receptor (FXR; NR1H4). Treatment of human hepatoma cells with either naturally occurring or synthetic [3-(2,6-dichlorophenyl)-4-(3′-carboxy-2-chloro-stilben-4-yl)-oxymethyl-5-isopropyl-isoxazole] FXR ligands resulted in the induction of transcripts for all three genes. The induction of FBGβ mRNA in response to activated FXR appears to be a primary transcriptional response, as it is blocked by actinomycin D but not by cycloheximide. Four FXR isoforms were recently identified that differ either at their N termini and/or by the presence of four amino acids in the hinge region. Interestingly, the activities of the human FBGβ promoter-reporter constructs were highly induced by FXR isoforms that lack the four amino acid insert.The observation that all three FBG subunits are induced by specific FXR isoforms, in response to FXR ligands, suggests that bile acids and FXR modulate fibrinolytic activity.http://www.sciencedirect.com/science/article/pii/S002222752034030Xfarnesoid X receptorchenodeoxycholic acid3-(2,6-dichlorophenyl)-4-(3′-carboxy-2-chloro-stilben-4-yl)-oxymethyl-5-isopropyl-isoxazolenuclear hormone receptor |
| spellingShingle | Andrew M. Anisfeld Heidi R. Kast-Woelbern Hans Lee Yanqiao Zhang Florence Y. Lee Peter A. Edwards Activation of the nuclear receptor FXR induces fibrinogen expression: a new role for bile acid signaling Journal of Lipid Research farnesoid X receptor chenodeoxycholic acid 3-(2,6-dichlorophenyl)-4-(3′-carboxy-2-chloro-stilben-4-yl)-oxymethyl-5-isopropyl-isoxazole nuclear hormone receptor |
| title | Activation of the nuclear receptor FXR induces fibrinogen expression: a new role for bile acid signaling |
| title_full | Activation of the nuclear receptor FXR induces fibrinogen expression: a new role for bile acid signaling |
| title_fullStr | Activation of the nuclear receptor FXR induces fibrinogen expression: a new role for bile acid signaling |
| title_full_unstemmed | Activation of the nuclear receptor FXR induces fibrinogen expression: a new role for bile acid signaling |
| title_short | Activation of the nuclear receptor FXR induces fibrinogen expression: a new role for bile acid signaling |
| title_sort | activation of the nuclear receptor fxr induces fibrinogen expression a new role for bile acid signaling |
| topic | farnesoid X receptor chenodeoxycholic acid 3-(2,6-dichlorophenyl)-4-(3′-carboxy-2-chloro-stilben-4-yl)-oxymethyl-5-isopropyl-isoxazole nuclear hormone receptor |
| url | http://www.sciencedirect.com/science/article/pii/S002222752034030X |
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