Suzuki Yoshiro, Landowski Christopher P, Hediger Matthias A
Institute of Biochemistry and Molecular Medicine, University of Bern, CH-3012 Berne, Switzerland.
Annu Rev Physiol. 2008;70:257-71. doi: 10.1146/annurev.physiol.69.031905.161003.
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.
钙离子（Ca2+）对我们身体的众多生理功能至关重要。因此，通过肠道吸收、肾脏重吸收和骨吸收的协调，其体内平衡得以精细维持。已鉴定出Ca2+选择性上皮通道TRPV5和TRPV6，并揭示了它们的生理作用：TRPV5在肾脏最终的Ca2+重吸收中起重要作用，而TRPV6在肠道Ca2+吸收中起关键作用。TRPV5基因敲除小鼠表现出肾性漏钙性高钙尿症，并相应地上调其肠道TRPV6表达以补偿其负Ca2+平衡。相反，尽管TRPV6基因敲除小鼠存在严重的负Ca2+平衡，但它们并未表现出任何补偿机制，从而导致继发性甲状旁腺功能亢进。这些结果表明，在与Ca2+平衡紊乱相关的人类疾病如高钙尿症、骨质疏松症和维生素D抵抗性佝偻病中，TRPV5和TRPV6基因受到不同的调控。
