Similarly potent action of 1,25-dihydroxyvitamin D3 and its analogues, tacalcitol, calcipotriol, and maxacalcitol on normal human keratinocyte proliferation and differentiation

Similarly potent action of 1,25-dihydroxyvitamin D3 and its analogues, tacalcitol, calcipotriol, and maxacalcitol on normal human keratinocyte proliferation and differentiation
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DOI:
10.1016/s0923-1811(02)00136-6
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发表时间:
2003-02-01
影响因子:
4.6
通讯作者:
Iizuka, H
Iizuka, H
中科院分区:
医学3区
文献类型:
--
作者:
Takahashi, H;Ibe, M;Iizuka, H

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背景:活性维生素D3调节表皮角质形成细胞的增殖和分化。最近,局部维生素D3、他卡西醇、卡泊三醇和maxacalcitol被广泛用于银屑病。目的:观察1,25-二羟维生素D3(1,25(OH)2D 3)对培养的正常角质形成细胞(NHK)的作用,并与维生素D3类似物进行比较。方法:采用MTS、BrdU、H-3-TdR掺入法检测NHK细胞增殖活性。Western blot、PCR扩增及定量检测外披蛋白、转氨酶1、角蛋白5和角蛋白1的表达。此外,我们还进行了皮质细胞被膜(CE)形成试验。结果如下:1,25(OH)2D 3、他卡西醇、卡泊三醇和maxacalcitol以浓度依赖性方式降低NHK细胞增殖,在10(-7)M时观察到最大效应。活性维生素D3类似物的抗增殖作用无显著差异。1,25(OH)_2D_3及其类似物在mRNA和蛋白水平诱导了外皮蛋白和转氨酶1的表达。1,25(OH)2D 3及其类似物也能诱导CE的形成。这些化学品之间的效力无显著差异。角蛋白5和1的表达没有改变这些活性维生素D3类似物。结论:本研究表明,活性维生素D3类似物,他卡西醇,卡泊三醇,和maxacalcitol,抑制角质形成细胞增殖和诱导分化具有相似的效力。(C)2002年日本皮肤病研究学会。由Elsevier Science爱尔兰有限公司出版。保留所有权利。
Background: The active vitamin D3 regulates proliferation and differentiation of epidermal keratinocytes. Recently topical vitamin D3, tacalcitol, calcipotriol, and maxacalcitol are widely used for psoriasis. Objective: To examine the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on cultured normal keratinocytes (NHK) and compared its effect with those of various vitamin D3 analogues. Methods: Cell proliferation of NHK cells was analyzed by MTS, BrdU and H-3-thymidine incorporation. The expression of involucrin, transglutaminase 1, keratin 5 and keratin 1 was investigated by western blot and PCR amplification and quantitative assay. Furthermore, we performed cornified cell envelope (CE) formation assay. Results: 1,25(OH)2D3, tacalcitol, calcipotriol, and maxacalcitol decreased NHK cell proliferation in a concentration-dependent manner and the maximal effect was observed at 10(-7) M. There was no significant difference in the anti-protiferative effect among the active vitamin D3 analogues. The expression of involucrin and transglutaminase 1 were induced by 1,25(OH)2D3 and its analogues in mRNA and protein levels. CE formation was also induced by 1,25(OH)2D3 and its analogues. There was no significant difference in the potency among these chemicals. Keratin 5 and 1 expression was not altered by these active vitamin D3 analogues. Conclusions: The present study demonstrated that active vitamin D3 analogues, tacalcitol, calcipotriol, and maxacalcitol, suppress keratinocyte proliferation and induce differentiation with similar potency. (C) 2002 Japanese Society for Investigative Dermatology. Published by Elsevier Science Ireland Ltd. All rights reserved.