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

Biochim Biophys Acta. 2005 Dec 30;1732(1-3):31-7. doi: 10.1016/j.bbaexp.2006.01.003. Epub 2006 Jan 26.

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/FTFmu) 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/FTFmu, 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Bile Acids and Salts / metabolism*
  • Biological Transport
  • Blotting, Northern
  • Blotting, Western
  • Caco-2 Cells
  • Cells, Cultured
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Models, Genetic
  • Molecular Sequence Data
  • Organic Anion Transporters, Sodium-Dependent / genetics
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Regulatory Elements, Transcriptional / genetics
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Symporters / genetics
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Bile Acids and Salts
  • DNA-Binding Proteins
  • Nr5a2 protein, mouse
  • Organic Anion Transporters, Sodium-Dependent
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptors, Cytoplasmic and Nuclear
  • Symporters
  • Transcription Factors
  • fetoprotein transcription factor
  • sodium-bile acid cotransporter
  • DNA