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Vitamin A Up-Regulates Expression of Bone-Type Alkaline Phosphatase in Rat Small Intestinal Crypt Cell Line and Fetal Rat Small Intestine

Manuscript received 29 April 1998. Initial reviews completed 1 June 1998. Revision accepted 11 July 1998.

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

Department of Nutrition, School of Medicine, The University of Tokushima, Tokushima 770-8503, Japan and * Department of Internal Medicine, Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO 63110

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, RARbeta 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.

Key words: vitamin A, liver/bone/kidney alkaline phosphatase, IEC-6 cells, retinoid receptors, fetal rat small intestine.

The Journal of Nutrition Vol. 128 No. 11 November 1998, pp. 1869-1877
Copyright ©1998 by the American Society for Nutritional Sciences




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