FXR regulates organic solute transporters α and β in the adrenal gland, kidney, and intestine
Expression of the farnesoid X receptor (FXR; NR1H4) is limited to the liver, intestine, kidney, and adrenal gland. However, the role of FXR in the latter two organs is unknown. In the current study, we performed microarray analysis using RNA from H295R cells infected with constitutively active FXR....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2006-01-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520336695 |
| _version_ | 1818385419436294144 |
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| author | Hans Lee Yanqiao Zhang Florence Y. Lee Stanley F. Nelson Frank J. Gonzalez Peter A. Edwards |
| author_facet | Hans Lee Yanqiao Zhang Florence Y. Lee Stanley F. Nelson Frank J. Gonzalez Peter A. Edwards |
| author_sort | Hans Lee |
| collection | DOAJ |
| description | Expression of the farnesoid X receptor (FXR; NR1H4) is limited to the liver, intestine, kidney, and adrenal gland. However, the role of FXR in the latter two organs is unknown. In the current study, we performed microarray analysis using RNA from H295R cells infected with constitutively active FXR. Several putative FXR target genes were identified, including the organic solute transporters α and β (OSTα and OSTβ). Electromobility shift assays and promoter-reporter studies identified functional farnesoid X receptor response elements (FXREs) in the promoters of both human genes. These FXREs are conserved in both mouse genes. Treatment of wild-type mice with 3-(2,6-dichlorophenyl)-4-(3′-carboxy-2-chloro-stilben-4-yl)-oxymethyl-5-isopropyl-isoxazole (GW4064), a synthetic FXR agonist, induced OSTα and OSTβ mRNAs in the intestine and kidney. Both mRNAs were also induced when wild-type, but not FXR-deficient (FXR−/−), adrenals were cultured in the presence of GW4064. OSTα and OSTβ mRNA levels were also induced in the adrenals and kidneys of wild-type, but not FXR−/−, mice after the increase of plasma bile acids in response to the hepatotoxin α-naphthylisothiocyanate. Finally, overexpression of human OSTα and OSTβ facilitated the uptake of conjugated chenodeoxycholate and the activation of FXR target genes. These results demonstrate that OSTα and OSTβ are novel FXR target genes that are expressed in the adrenal gland, kidney, and intestine.—Lee, H., Y. Zhang, F. Y. Lee, S. F. Nelson, F. J. Gonzalez, and P. A. Edwards. FXR regulates organic solute transporters α and β in the adrenal gland, kidney, and intestine. |
| first_indexed | 2024-12-14T03:37:51Z |
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| id | doaj.art-9ce19830751d4a7f840ce3c4d5af34a3 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T03:37:51Z |
| publishDate | 2006-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-9ce19830751d4a7f840ce3c4d5af34a32022-12-21T23:18:34ZengElsevierJournal of Lipid Research0022-22752006-01-01471201214FXR regulates organic solute transporters α and β in the adrenal gland, kidney, and intestineHans Lee0Yanqiao Zhang1Florence Y. Lee2Stanley F. Nelson3Frank J. Gonzalez4Peter A. Edwards5Department of Biological Chemistry and Medicine, University of California, Los Angeles, Los Angeles, CA 90095; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095; Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892Department of Biological Chemistry and Medicine, University of California, Los Angeles, Los Angeles, CA 90095; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095; Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892Department of Biological Chemistry and Medicine, University of California, Los Angeles, Los Angeles, CA 90095; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095; Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892Department of Biological Chemistry and Medicine, University of California, Los Angeles, Los Angeles, CA 90095; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095; Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892Department of Biological Chemistry and Medicine, University of California, Los Angeles, Los Angeles, CA 90095; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095; Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892Department of Biological Chemistry and Medicine, University of California, Los Angeles, Los Angeles, CA 90095; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095; Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892Expression of the farnesoid X receptor (FXR; NR1H4) is limited to the liver, intestine, kidney, and adrenal gland. However, the role of FXR in the latter two organs is unknown. In the current study, we performed microarray analysis using RNA from H295R cells infected with constitutively active FXR. Several putative FXR target genes were identified, including the organic solute transporters α and β (OSTα and OSTβ). Electromobility shift assays and promoter-reporter studies identified functional farnesoid X receptor response elements (FXREs) in the promoters of both human genes. These FXREs are conserved in both mouse genes. Treatment of wild-type mice with 3-(2,6-dichlorophenyl)-4-(3′-carboxy-2-chloro-stilben-4-yl)-oxymethyl-5-isopropyl-isoxazole (GW4064), a synthetic FXR agonist, induced OSTα and OSTβ mRNAs in the intestine and kidney. Both mRNAs were also induced when wild-type, but not FXR-deficient (FXR−/−), adrenals were cultured in the presence of GW4064. OSTα and OSTβ mRNA levels were also induced in the adrenals and kidneys of wild-type, but not FXR−/−, mice after the increase of plasma bile acids in response to the hepatotoxin α-naphthylisothiocyanate. Finally, overexpression of human OSTα and OSTβ facilitated the uptake of conjugated chenodeoxycholate and the activation of FXR target genes. These results demonstrate that OSTα and OSTβ are novel FXR target genes that are expressed in the adrenal gland, kidney, and intestine.—Lee, H., Y. Zhang, F. Y. Lee, S. F. Nelson, F. J. Gonzalez, and P. A. Edwards. FXR regulates organic solute transporters α and β in the adrenal gland, kidney, and intestine.http://www.sciencedirect.com/science/article/pii/S0022227520336695farnesoid X receptorchenodeoxycholic acid3-(2,6-dichlorophenyl)-4-(3′carboxy-2-chloro-stilben-4-yl)-oxymethyl-5-isopropyl-isoxazole |
| spellingShingle | Hans Lee Yanqiao Zhang Florence Y. Lee Stanley F. Nelson Frank J. Gonzalez Peter A. Edwards FXR regulates organic solute transporters α and β in the adrenal gland, kidney, and intestine 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 |
| title | FXR regulates organic solute transporters α and β in the adrenal gland, kidney, and intestine |
| title_full | FXR regulates organic solute transporters α and β in the adrenal gland, kidney, and intestine |
| title_fullStr | FXR regulates organic solute transporters α and β in the adrenal gland, kidney, and intestine |
| title_full_unstemmed | FXR regulates organic solute transporters α and β in the adrenal gland, kidney, and intestine |
| title_short | FXR regulates organic solute transporters α and β in the adrenal gland, kidney, and intestine |
| title_sort | fxr regulates organic solute transporters α and β in the adrenal gland kidney and intestine |
| topic | farnesoid X receptor chenodeoxycholic acid 3-(2,6-dichlorophenyl)-4-(3′carboxy-2-chloro-stilben-4-yl)-oxymethyl-5-isopropyl-isoxazole |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520336695 |
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