EFFECTS OF 1,25-DIHYDROXYVITAMIN-D(3) ON PROLIFERATION AND DIFFERENTIATION OF CACO-2 CELLS

EFFECTS OF 1,25-DIHYDROXYVITAMIN-D(3) ON PROLIFERATION AND DIFFERENTIATION OF CACO-2 CELLS
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DOI:
10.1210/en.134.4.1710
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发表时间:
1994-04-01
期刊:
影响因子:
4.8
通讯作者:
BRASITUS, TA
BRASITUS, TA
中科院分区:
医学2区
文献类型:
--
作者:
HALLINE, AG;DAVIDSON, NO;BRASITUS, TA

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研究了1,25-二羟基维生素D3 [1,25-(OH)2D 3]或骨化三醇对Caco-2细胞增殖和分化的影响。维生素D受体mRNA检测前和汇合后的细胞,其丰度随时间和响应骨化三醇不变。1,25-(OH)2D 3结合活性在分化过程中增加,但1,25-(OH)2D 3处理的细胞和对照细胞之间的结合没有差异。通过[H-3]胸苷掺入和DNA含量评估,1,25-(OH)2D 3导致增殖呈剂量依赖性降低。1,25-(OH)_2D_3显著增强了分化过程中碱性磷酸酶活性的正常升高,并增加了碱性磷酸酶mRNA的丰度。相反,1,25-(OH)2D 3抑制蔗糖酶-异麦芽糖酶活性和相应mRNA水平的正常升高,尽管这种抑制发生在细胞分化的初始阶段之后(接种后>10天)。形态学分析表明,1,25-(OH)_2D_3在接种后12天增加了平均圆顶直径和微绒毛长度和密度。虽然1,25-(OH)2D 3降低Caco-2细胞的增殖并增强某些分化参数,但并非所有刷状缘水解酶都以类似的方式响应,因此有必要谨慎解释其作为分化标志物的单独使用。
The effect of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], or calcitriol, on the proliferation and differentiation of Caco-2 cells was studied. Vitamin D receptor mRNA was detected in both pre- and postconfluent cells, and its abundance was unchanged with time and in response to calcitriol. 1,25-(OH)2D3-binding activity increased during differentiation, but there was no difference in binding between 1,25-(OH)2D3-treated and control cells. 1,25-(OH)2D3 caused a dose-dependent reduction in proliferation, as assessed by [H-3]thymidine incorporation and DNA content. 1,25-(OH)2D3 significantly enhanced the normal rise in alkaline phosphatase activity during differentiation and increased alkaline phosphatase mRNA abundance. In contrast, 1,25-(OH)2D3 inhibited the normal rise in sucrase-isomaltase activity and the corresponding mRNA level, although the inhibition occurred after the initial period of cell differentiation (>10 days postplating). Morphological analysis demonstrated that by day 12 postplating, 1,25-(OH)2D3 increased the mean dome diameter and microvillus length and density. Although 1,25-(OH)2D3 decreases the proliferation of Caco-2 cells and enhances certain parameters of differentiation, not all brush-border hydrolases respond in a similar fashion, making it necessary to interpret with caution their individual use as markers of differentiation.