Analysis of vitamin D-dependent calcium-binding protein messenger ribonucleic acid expression in mice lacking the vitamin D receptor.
Analysis of vitamin D-dependent calcium-binding protein messenger ribonucleic acid expression in mice lacking the vitamin D receptor.
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DOI：
10.1210/endo.139.3.5803
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发表时间：
1998-03
期刊：
影响因子：
4.8
通讯作者：
Yan Chun Li;A. Pirro;M. Demay
中科院分区：
文献类型：
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作者：
Yan Chun Li;A. Pirro;M. Demay
为了研究1，25-二羟维生素D3 [1，25-（OH）2D 3]在调节维生素D依赖性钙结合蛋白（calbindin-D）中的受体依赖性作用，检测了维生素D受体（VDR）消融小鼠和对照同窝仔中calbindin-D9 k和-28k的信使RNA（mRNA）水平。在VDR消融小鼠中，肠、肾、肺和脑中的钙结合蛋白-D9 k mRNA显著降低;然而，肾脏中的钙结合蛋白-D28 k mRNA仅中度降低。注射1，25-（OH）2D 3后，对照动物中的钙结合蛋白-D9 k mRNA水平以及肾脏和肺泡钙结合蛋白-D28 k mRNA水平被诱导，但在纯合子小鼠中未被诱导。当给小鼠喂食高乳糖、钙和磷的饮食时，纯合子小鼠的肠道钙结合蛋白-D9 k mRNA水平恢复到对照组小鼠的水平。然而，这种饮食未能使肠外钙结合蛋白mRNA水平正常化。这些发现表明，受体依赖性行动的1，25-（OH）2D 3调节calbindin-D9 k基因的表达和组织特异性因素调节的影响，1，25-（OH）2D 3对calbindin-D28 k基因的表达。这些数据还表明，在功能性VDR不存在的情况下，肠腔中高局部浓度的钙、磷和/或乳糖可以使肠钙结合蛋白-D9 k mRNA水平正常化。
To investigate the roles of the receptor-dependent actions of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in the regulation of vitamin D-dependent calcium-binding proteins (calbindin-D), the messenger RNA (mRNA) levels of calbindin-D9k and -28k were examined in vitamin D receptor (VDR)-ablated mice and control littermates. In VDR-ablated mice, calbindin-D9k mRNA was dramatically reduced in the intestine, kidneys, lungs, and brain; however, calbindin-D28k mRNA was only moderately decreased in the kidney. After 1,25-(OH)2D3 injection, calbindin-D9k mRNA levels and renal and alveolar calbindin-D28k mRNA levels were induced in control animals, but not in the homozygous mice. When the mice were fed a diet high in lactose, calcium, and phosphorus, intestinal calbindin-D9k mRNA levels in the homozygous mice were restored to those in their control littermates. However, this diet failed to normalize extraintestinal calbindin mRNA levels. These findings demonstrate that the receptor-dependent actions of 1,25-(OH)2D3 regulate calbindin-D9k gene expression and that tissue-specific factors modulate the effects of 1,25-(OH)2D3 on calbindin-D28k gene expression. These data also demonstrate that in the absence of a functional VDR, a high local concentration of calcium, phosphorus, and/or lactose in the intestinal lumen can normalize intestinal calbindin-D9k mRNA levels.