Abstract
Calcium absorption is regulated by both active (transcellular) and passive (paracellular) pathways. Although each pathway has been studied, correlations between the two pathways have not been well elucidated. In previous investigations, the critical transcellular proteins, calbindin-D9k (CaBP-9k) and -D28k (CaBP-28k), were shown to affect other transcellular pathways by buffering intracellular calcium concentrations. The rate of paracellular calcium transport in the duodenum is generally determined by the expression of tight junction genes. In the present study, the effect of dietary calcium and/or vitamin D supplementation on the expression of tight junction genes (occludin, ZO-1 and claudin 2, 10b, 12 and 15) in the duodenum of CaBP-9k- and/or -28k-deficient mice was examined. With a normal diet, the expression of most tight junction genes in the duodenum was significantly increased in CaBP-9k knockout (KO) mice compared to wild-type (WT) animals. With a calcium- and vitamin D-deficient diet, tight junction gene expression was significantly decreased in the duodenum of the CaBP-9k KO mice. These findings suggest that expression of paracellular tight junction genes is regulated by transcellular CaBP proteins, suggesting that active and passive calcium transport pathways may function cooperatively.
Highlights
Calcium is involved in many functions, such as intracellular signaling, blood clotting and muscle contraction, making this mineral essential for maintaining life
Serum calcium concentrations according to genotype and diet were first examined
Calcium concentrations were decreased below normal ranges in WT, CaBP-28k KO and double KO (DKO) mice fed the calcium/vitamin D-deficient diet
Summary
Calcium is involved in many functions, such as intracellular signaling, blood clotting and muscle contraction, making this mineral essential for maintaining life. Tight junctions are involved in several different processes, such as cell adhesion, intracellular signaling, protection from extracellular invasion and paracellular transport [12]. These junctions are composed of transmembrane proteins, cytoskeleton components and cytoplasmic plaques [13]. Among the various tight junction proteins, transmembrane proteins and cytoplasmic plaques are important for paracellular transport. Junction adhesion molecules (JAMs), occludin (OCLN) and claudin (CLDN) are representative transmembrane proteins [14]. Non-selective and charge-selective ion transport are governed by the expression of transmembrane proteins [15]. D-deficient diets in order to further investigate the functions of tight junction genes in calcium absorption
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