PTH regulates expression of ClC-5 chloride channel in the kidney.
PTH regulates expression of ClC-5 chloride channel in the kidney.
复制标题
PTH 调节肾脏中 ClC-5 氯离子通道的表达。
DOI：
10.1152/ajprenal.2000.278.2.f238
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Guggino,WB
中科院分区：
文献类型：
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作者：
Silva,IV;Blaisdell,CJ;Guggino,SE;Guggino,WB
氯离子通道ClC-5的突变已在几种导致肾结石形成的遗传性疾病中被描述。为了确定ClC-5是否也参与钙稳态，我们研究了在切除甲状旁腺和不切除甲状旁腺后，缺乏1α，25(OH)2维生素d3的大鼠中，ClC-5 mRNA和蛋白表达是否受到调节。部分动物替代甲状旁腺激素（PTH）。与对照动物相比，维生素d缺乏、去甲状旁腺的大鼠血清和尿钙浓度较低，血清甲状旁腺素和降钙素浓度也较低。与对照组和维生素d缺乏动物相比，维生素d缺乏、去甲状旁腺的大鼠皮层ClC-5 mRNA和蛋白水平降低。注射甲状旁腺激素后，在维生素d缺乏、甲状旁腺切除的大鼠中，ClC-5 mRNA和蛋白表达接近控制水平。各组大鼠髓质中ClC-5 mRNA及蛋白表达均未见明显变化。我们的研究结果表明，PTH调节肾皮质中ClC-5的表达，而1α，25(OH)2维生素d3和PTH均不调节肾髓质中ClC-5的表达。ClC-5的表达模式随尿钙的变化而变化。尿钙浓度较高的动物，其ClC-5 mRNA和蛋白表达水平较低，提示ClC-5氯离子通道在钙重吸收中起作用。
Mutations in the chloride channel, ClC-5, have been described in several inherited diseases that result in the formation of kidney stones. To determine whether ClC-5 is also involved in calcium homeostasis, we investigated whether ClC-5 mRNA and protein expression are modulated in rats deficient in 1α,25(OH)2vitamin D3with and without thyroparathyroidectomy. Parathyroid hormone (PTH) was replaced in some animals. Vitamin D-deficient, thyroparathyrodectomized rats had lower serum and higher urinary calcium concentrations compared with control animals as well as lower serum PTH and calcitonin concentrations. ClC-5 mRNA and protein levels in the cortex decrease in vitamin D-deficient, thyroparathyroidectomized rats compared with both control and vitamin D-deficient animals. ClC-5 mRNA and protein expression increase near to control levels in vitamin D-deficient, thyroparathyroidectomized rats injected with PTH. No significant changes in ClC-5 mRNA and protein expression in the medulla were detected in any experimental group. Our results suggest that PTH modulates the expression of ClC-5 in the kidney cortex and that neither 1α,25(OH)2vitamin D3nor PTH regulates ClC-5 expression in the medulla. The pattern of expression of ClC-5 varies with urinary calcium. Animals with higher urinary calcium concentrations have lower levels of ClC-5 mRNA and protein expression, suggesting that the ClC-5 chloride channel plays a role in calcium reabsorption.