Regulation of the sodium/sulfate co-transporter by farnesoid X receptor α

Hans Lee, Melissa L. Hubbert, Timothy Osborne, Katherine Woodford, Noa Zerangue, Peter A. Edwards

Research output: Contribution to journalArticle

Abstract

Fxrα is known to regulate a variety of metabolic processes, including bile acid, cholesterol, and carbohydrate metabolism. In this study, we show direct evidence that Fxrα is a key player in maintaining sulfate homeostasis. We identified and characterized the sodium/sulfate co-transporter (NaS-1; Slc13a1) as an Fxrα target gene expressed in the kidney and intestine. Electromobility shift assays, chromatin immunoprecipitation, and promoter reporter studies identified a single functional Fxrα response element in the second intron of the mouse Slc13a1 gene. Treatment of wild-type mice with GW4064, a synthetic Fxrα agonist, induced Slc13a1 mRNA in the intestine and kidney. Slc13a1mRNAwas also induced in the kidney and intestine of wild-type, but not Fxrα-/- mice, after treatment with the hepatotoxin α-naphthylisothiocyanate, which is known to result in elevated blood bile acid levels. Finally, we observed a decrease in Slc13a1 mRNA in the kidney and intestine of Fxrα-/- mice and a corresponding increase in urinary excretion of free sulfates as compared with wild-type mice. These results demonstrate that mouse Slc13a1 is a novel Fxrα target gene expressed in the kidney and intestine and that in the absence of Fxrα, mice waste sulfate into the urine. Thus, Fxrα is necessary for normal sulfate homeostasis in vivo.

Original languageEnglish (US)
Pages (from-to)21653-21661
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number30
DOIs
StatePublished - Jul 27 2007
Externally publishedYes

Fingerprint

Symporters
Sulfates
Intestines
Genes
Bile Acids and Salts
Kidney
Messenger RNA
Response Elements
Introns
Homeostasis
Chromatin
Assays
Blood
Cholesterol
Chromatin Immunoprecipitation
Carbohydrate Metabolism
sodium sulfate
Urine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lee, H., Hubbert, M. L., Osborne, T., Woodford, K., Zerangue, N., & Edwards, P. A. (2007). Regulation of the sodium/sulfate co-transporter by farnesoid X receptor α. Journal of Biological Chemistry, 282(30), 21653-21661. https://doi.org/10.1074/jbc.M700897200

Regulation of the sodium/sulfate co-transporter by farnesoid X receptor α. / Lee, Hans; Hubbert, Melissa L.; Osborne, Timothy; Woodford, Katherine; Zerangue, Noa; Edwards, Peter A.

In: Journal of Biological Chemistry, Vol. 282, No. 30, 27.07.2007, p. 21653-21661.

Research output: Contribution to journalArticle

Lee, H, Hubbert, ML, Osborne, T, Woodford, K, Zerangue, N & Edwards, PA 2007, 'Regulation of the sodium/sulfate co-transporter by farnesoid X receptor α', Journal of Biological Chemistry, vol. 282, no. 30, pp. 21653-21661. https://doi.org/10.1074/jbc.M700897200
Lee, Hans ; Hubbert, Melissa L. ; Osborne, Timothy ; Woodford, Katherine ; Zerangue, Noa ; Edwards, Peter A. / Regulation of the sodium/sulfate co-transporter by farnesoid X receptor α. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 30. pp. 21653-21661.
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