Developmental Expression of Calcitriol Receptors, 9-Kilodalton Calcium-Binding Protein, and Calcidiol 24-Hydroxylase in Human Intestine

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.

Factors involved in the duodenal expression of the human calbindin-D9k gene

“…Intestinal expression of calbindin-D9k occurs proximally in the duodenum and not more distally. Previously this has been shown in adult human intestine for the protein [9] and for RNA and protein in fetal gut [31]. We confirmed this distribution of mRNA in adult human intestine ( Figure 3A), and in rat small intestine, where expression is abundant only in the most proximal segment ( Figure 3B).…”

Expression of vitamin D receptor and vitamin D status in patients with oral neoplasms and effect of vitamin D supplementation on quality of life in advanced cancer treatment

“…There are very few studies on VDR expression in oral neoplastic tissue in in vivo and ex vivo settings [ 43 ]. Published papers hypothesize that calcitriol enhances VDR expression at gene and protein levels in vitro in renal and various non-renal tissues in the body, including the colon [ 44 , 45 ], breast [ 46 , 47 ] and prostrate [ 48 ]. Moreover, it is thought that inflammatory peptides/cytokines expressed by tumor-infiltrating leukocytes and oral premalignant/ tumor cells also up-regulate VDR expression in adjacent cells [ 49 ].…”

Enteral Nutrient Supply for Preterm Infants: Commentary From the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition

“…There is evidence that, as early as in the 20th week of gestation, the human foetal intestine possesses functional calcitriol receptors that regulate the expression of calcium-binding protein and calcidiol-24-hydroxylase (42,43). In contrast to Brenner's study (41), Senterre et al (44) have shown, by performing 3-day metabolic balances, that calcium net absorption increased from 50% to 71% by feeding appropriate-for-gestational age preterm infants weighing <1500 g banked human milk alone or supplemented with 30 mg of cholecalciferol/day (1200 IU) without calcium fortification.…”