Mechanisms and Regulation of Epithelial Ca²⁺ Absorption in Health and Disease

Ca²⁺ is essential for numerous physiological functions in our bodies. Therefore, its homeostasis is finely maintained through the coordination of intestinal absorption, renal reabsorption, and bone resorption. The Ca²⁺-selective epithelial channels TRPV5 and TRPV6 have been identified, and their physiological roles have been revealed: TRPV5 is important in final renal Ca²⁺ reabsorption, and TRPV6 has a key role in intestinal Ca²⁺ absorption. The TRPV5 knockout mice exhibit renal leak hypercalciuria and accordingly upregulate their intestinal TRPV6 expression to compensate for their negative Ca²⁺ balance. In contrast, despite their severe negative Ca²⁺ balance, TRPV6-null mice do not display any compensatory mechanism, thus resulting in secondary hyperparathyroidism. These results indicate that the genes for TRPV5 and TRPV6 are differentially regulated in human diseases associated with disturbed Ca²⁺ balance such as hypercalciuria, osteoporosis, and vitamin D–resistant rickets.