FTF and LRH-1, two related but different transcription factors in human Caco-2 cells: Their different roles in the regulation of bile acid transport

Debra H. Pan, Frank Chen, Ezequiel Neimark, Xiaoping Li, Benjamin L. Shneider

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The apical sodium dependent bile acid transporter (ASBT) mediates ileal bile acid reabsorption. The transcription factors, liver receptor homologue-1 (LRH-1:mouse) and fetoprotein transcription factor (FTF:human), are presumably orthologues. Bile-acid induced negative feedback regulation of mouse (m) and human (h) ASBT occurs via LRH-1 and RAR/RXR, respectively. hASBT has a potential FTF cis-element, although its functional role is unknown. hASBT and mASBT promoter constructs and an FTF cis-element mutated hASBT (hASBT/FTFμ) were assessed in human Caco-2 cells treated with chenodeoxycholic acid (CDCA) and/or co-transfected with hFTF, mLRH-1, or specific small interfering FTF or LRH-1 RNA (siFTF or siLRH). Basal promoter activity was reduced in hASBT/FTFμ, although bile acid response persisted. hFTF activated hASBT but not mASBT, while mLRH-1 activated mASBT but not hASBT. siFTF reduced hASBT but not mASBT activity; siLRH reduced mASBT but not hASBT activity. siLRH but not siFTF abrogated bile acid responsiveness. Electrophoretic mobility shift assays demonstrated distinct and specific binding of the mLRH-1 or hFTF cis-elements. In conclusion, FTF and LRH-1 are two related but different transcription factors in human Caco-2 cells, suggesting that they may be homologues and not orthologues. FTF is not involved directly in bile acid mediated negative feedback regulation of the ASBT.

Original languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Volume1732
Issue number1-3
DOIs
StatePublished - Dec 30 2005
Externally publishedYes

Keywords

  • Enterohepatic
  • Ileum
  • Liver
  • Nuclear receptor
  • Transcription

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Genetics

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