Vitamin a up-regulates expression of bone-type alkaline phosphatase in a rat small intestinal crypt cell line and fetal rat small intestine

Takeshi Nikawa, Kazuhito Rokutan, Kayo Nanba, Kaori Tokuoka, Shigetada Teshima, Michael J. Engle, David H. Alpers, Kyoichi Kishi

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Abstract

Vitamin A is a potent inducer for liver/bone/kidney alkaline phosphatase (L/B/K ALP) in a variety of tissues. However, the evidence for induction of L/B/K ALP by vitamin A in small intestine is limited. In this study, we investigated the influence of vitamin A on L/B/K ALP expression in rat small intestinal crypt IEC-6 cells and fetal rat small intestine. Treatment of IEC- 6 cells with all-trans retinoic acid (RA) increased the levels of activity, protein and mRNA of L/B/K ALP, whereas enterocyte-specific proteins, including intestinal ALP, sucrase-isomaltase and glucose transporter-2, were not induced. The reverse transcription-polymerase chain reaction technique revealed that this L/B/K ALP transcript had the bone-type but not the liver- type leader exon. IEC-6 cells constitutively expressed mRNAs of all subtypes of retinoic acid receptor (RAR) and retinoid X receptor (RXR) at varied concentrations. Among these receptor mRNAs, RARβ mRNA quickly responded to RA treatment, and the level was doubled within 4 h. Gel mobility shift assay showed that RA induced an RXRE-binding activity in IEC-6 cells. The L/B/K ALP transcript, expressed in fetal rat small intestine, also contained the bone- type leader exon. Intragastric administration of 10 mg retinyl acetate to pregnant rats from gestational d 7 to 15 increased the levels of this transcript and enzyme in 15-d fetal rat small intestine. Our results suggest that vitamin A may be an important regulator for L/B/K ALP expression in fetal rat small intestine as well as in IEC-6 cells.

Original languageEnglish
Pages (from-to)1869-1877
Number of pages9
JournalJournal of Nutrition
Volume128
Issue number11
StatePublished - Nov 1 1998

Keywords

  • Fetal rat small intestine
  • IEC-6 cells
  • Liver/bone/kidney alkaline phosphatase
  • Retinoid receptors
  • Vitamin A

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    Nikawa, T., Rokutan, K., Nanba, K., Tokuoka, K., Teshima, S., Engle, M. J., Alpers, D. H., & Kishi, K. (1998). Vitamin a up-regulates expression of bone-type alkaline phosphatase in a rat small intestinal crypt cell line and fetal rat small intestine. Journal of Nutrition, 128(11), 1869-1877.