Abstract
Human intestinal mucosa consists of highly active epithelial cells in continual renewal and differentiation processes located at different portions of the villi. The crypt contains abundant replicating cells which, upon reaching the villus tip, acquire their fully differentiated state. Besides its well recognized role in bone cell homeostasis, calcitriol has been attributed a role in cellular differentiation and proliferation in normal leukocytes and myeloid leukemia cells. We have previously documented the presence and the distribution of specific calcitriol receptors in the cells of the small and large intestine from 13-20-wk-old human fetuses and that calcitriol was able to promote human intestinal epithelium proliferation or differentiation, in organ culture, depending upon fetal age. We now show that, whereas transcripts for calcitriol receptors are abundant from duodenum to colon, those for the 9-kD calcium-binding protein are present mainly in the duodenum and the jejunum and to a lesser extent in the ileum and the colon. Transcripts for 25-hydroxycholecalciferol-24-hydroxylase could not be detected in any of the intestine segments despite a prolonged exposition of the gels. Immunofluorescence staining for the 9-kD calcium-binding protein was exclusively observed in the epithelial cells of the small intestine and colon, the subepithelial layers being always negative. The 9-kD calcium-binding protein distribution along the crypt-villus axis appeared as a gradient, increasing from the developing crypt to the tip of the villus in the duodenum, jejunum, and ileum. Based on the present observations and on the fact that calcitriol promotes human fetal proliferation and differentiation, the presence of transcripts for calcitriol receptors and 9-kD calcium-binding protein in the intestinal cell opens interesting possibilities as of their role in the in utero human gut development and the control of colorectal cancers.
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Abbreviations
- CaBP:
-
calcium-binding protein
- VDR:
-
calcitriol receptor
- 24-OHase:
-
calcidiol-24-hydroxylase
- GAPDH:
-
glyceraldehyde-3-phosphate dehydrogenase
- PCR:
-
polymerase chain reaction
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Acknowledgements
The authors thank Dr. Michael Staun from the Medical Department (Gastroenterology) Rigshospitalet, Copenhagen, Denmark, for his generous gift of the MAb against human calcium-binding protein, and Dr. John Krisinger from the Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada, for kindly providing the full-length cDNA encoding the human 9-kD calbindin. We gratefully acknowledge the expert technical contribution of Lina Corriveau in setting up the organ cultures.
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Supported by the Medical Research Council of Canada (MT 11709 to E.E.D.) and le Centre de recherche de l'Hôpital Sainte-Justine.
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Delvin, E., Lopez, V., Levy, E. et al. Developmental Expression of Calcitriol Receptors, 9-Kilodalton Calcium-Binding Protein, and Calcidiol 24-Hydroxylase in Human Intestine. Pediatr Res 40, 664–670 (1996). https://doi.org/10.1203/00006450-199611000-00004
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DOI: https://doi.org/10.1203/00006450-199611000-00004
