Abstract
Calbindin-D9k (CaBP-9k) binds calcium with high affinity and regulates the distribution of free calcium in the cytoplasm. The expression of CaBP-9k is detected primarily in intestine that is vitamin D target tissue, and accumulates in the enterocytes of the duodenal villi. These enterocytes are the clearest example of vitamin D responsive cells, and the presence of CaBP-9k within them accentuates calcium absorption mediated by active transcellular calcium transport. It has been well established that the expression of CaBP-9k is mediated with vitamin D response element on its promoter and it regulates the amount of intracellular calcium in order to prevent cell death from reaching the toxicity of free calcium. There is now little doubt that glucocorticoid also decreases CaBP-9k expression in duodenal epithelial cells. In addition, it was reported that the level of CaBP-9k gene in enterocytes is increased in pregnancy when the plasma estradiol concentration is generally associated with a concomitant increase. Although calcium homeostasis was not disturbed in mice lacking the CaBP-9k gene, we found that CaBP-9k has a buffering role of free calcium in the cytosolic environment beyond that of calcium transfer. To expand our knowledge of the biological functions of CaBP-9k, our research has focused on defining the biological significance of intracellular CaBP-9k. Our findings suggest that the CaBP-9k gene is involved in compensatory induction of other calcium transporter genes in duodenal epithelial cells. This article summarizes the findings from recent studies on the expression and the functions of CaBP-9k in the small intestine.
Highlights
Calcium homeostasis refers to the regulation of the concentration of calcium ions in the body, and impairment of this mechanism contributes to their underlying pathologies, such as hypercalcemia or hypocalcemia
CaBP-9k presents in the majority of the intestinal epithelium as shown in Figure 2, and this suggest that mouse CaBP-9k in the duodenum might be confined to enterocytes, the major population of duodenal epithelial cells, because other cell types in the epithelium are present in 2%–3% population of epithelial cells in the villus
The expression of transient receptor potential vanilloid 6 (TRPV6) and plasma membrane Ca2+-ATPase 1b (PMCA1b) revealed a compensatory increase in CaBP-9k null mice as shown in Figure 3, and their inductions are reduced by exogenous glucocorticoid, which regulates duodenal vitamin D receptor (VDR) transcription in CaBP-9k null mice [49]
Summary
Calcium homeostasis refers to the regulation of the concentration of calcium ions in the body, and impairment of this mechanism contributes to their underlying pathologies, such as hypercalcemia or hypocalcemia. In order to understand the influence of CaBP-9k related to other calcium related proteins, we focused our attention on the expression and function of CaBP-9k within duodenal epithelial cells. The jejunum and ileum are other sites of dietary calcium absorption via paracellular absorption [8,9], the presence of calcium-related proteins in duodenal epithelial cells promotes uptake of calcium across the epithelium and its transport into the blood stream via transcellular absorption. CaBP-9k presents in the majority of the intestinal epithelium as shown, and this suggest that mouse CaBP-9k in the duodenum might be confined to enterocytes, the major population of duodenal epithelial cells, because other cell types in the epithelium are present in 2%–3% population of epithelial cells in the villus. HNF-4α (nuclear protein marker, G, Red) used in an attempt to identify the GR (H, green) expression in duodenal enterocytes, both images were merged and observed as blue (I).
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