Regulation of tight junction gene expression in the kidney of calbindin-D9k and/or -D28k knockout mice after consumption of a calcium- or a calcium/vitamin D-deficient diet

钙结合蛋白-D9k 和/或 -D28k 基因敲除小鼠摄入缺钙或缺钙/维生素 D 饮食后,肾脏中紧密连接基因表达的调控

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Abstract

BACKGROUND: Calciotropic hormones were thought to facilitate calcium transfer through active transcellular or passive paracellular pathway for calcium homeostasis. While calcium transport proteins such as CaBP-28 k, TRPV5, NCX1, PMCA1b are involved in calcium reabsorption of the renal tubule using transcellular transport, tight junction proteins are known as critically related to calcium absorption through paracellular pathway. The regulation of each pathway for calcium transport was well studied but the correlation was not. It is expected that present study will provide new information about the link between transcellular and paracellular pathway within renal tubules. RESULTS: Transcripts and proteins of tight junction related genes (occludin, ZO-1, and claudins) were examined in CaBP-9 k-and/or-28 k-deficient mice as well as the effect of dietary calcium and/or vitamin D supplementation. With a normal diet, the transcriptional and translational expressions of most tight junction proteins in the kidney was not significantly changed but with a calcium- and vitamin D-deficient diet, and they were significantly increased in the kidney of the CaBP-28 k and CaBP-9 k/28 k double KO (DKO) mice. In these genotypes, the increase of tight junction related transcripts and proteins are referred to as an evidence explaining correlation between transcellular transport and paracellular pathway. CONCLUSIONS: These findings are particularly interesting in evidences that insufficient transcellular calcium transports are compensated by paracellular pathway in calcium or calcium/vitamin D deficient condition, and that both transcellular and paracellular pathways functionally cooperate for calcium reabsorption in the kidney.

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