Calcium and 1,25(OH)2D:: interacting drivers of epidermal differentiation
Calcium and 1,25(OH)2D:: interacting drivers of epidermal differentiation
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DOI：
10.1016/j.jsbmb.2004.03.020
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发表时间：
2004-05-01
影响因子：
4.1
通讯作者：
Xie, Z
中科院分区：
文献类型：
--
作者：
Bikle, DD;Oda, Y;Xie, Z
钙离子和1，25（OH）（2）D均能促进角质形成细胞的分化。角质形成细胞自分泌或旁分泌产生1，25（OH）（2）D，结合表皮钙梯度在体内调节角质形成细胞分化中的关键作用，表明这种相互作用的生理重要性。这些相互作用发生在多个层面上。钙和1，25（OH）（2）D协同诱导外皮蛋白，外皮蛋白是一种对皮层包膜形成至关重要的蛋白质。外皮蛋白启动子含有钙和1，25（OH）（2）D诱导所必需的AP-1位点和邻近的1，25（OH）（2）D诱导所必需的VDRE，但不是钙诱导。钙调节与维生素D受体（VDR）结合的辅激活因子复合物。来自在低钙中生长的细胞的核提取物含有丰富的DRIP 205，而钙诱导的分化导致DRIP 205减少和SRC 3增加，SRC 3在其与VDR的结合中取代DRIP。体内模型支持1，25（OH）（2）D-钙相互作用在表皮分化中的重要性。1alphaOHase基因敲除小鼠的表皮不能形成正常的钙梯度，对屏障功能至关重要的蛋白质表达减少，并且当破坏时，渗透性屏障几乎没有恢复。因此，在体内和体外，钙和1，25（OH）（2）D在多个水平上相互作用，以调节表皮分化。(C)2004爱思唯尔有限公司保留所有权利。
Both calcium and 1,25(OH)(2)D promote the differentiation of keratinocytes in vitro. The autocrine or paracrine production of 1,25(OH)(2)D by keratinocytes combined with the critical role of the epidermal calcium gradient in regulating keratinocyte differentiation in vivo suggest the physiologic importance of this interaction. The interactions occur at a number of levels. Calcium and 1,25(OH)(2)D synergistically induce involucrin, a protein critical for cornified envelope formation. The involucrin promoter contains an AP-1 site essential for calcium and 1,25(OH)(2)D induction and an adjacent VDRE essential for 1,25(OH)(2)D but not calcium induction. Calcium regulates coactivator complexes that bind to the Vitamin D receptor (VDR). Nuclear extracts from cells grown in low calcium contain an abundance of DRIP205, whereas calcium induced differentiation leads to reduced DRIP205 and increased SRC 3 which replaces DRIP in its binding to the VDR. In vivo models support the importance of 1,25(OH)(2)D-calcium interactions in epidermal differentiation. The epidermis of 1alphaOHase null mice fails to form a normal calcium gradient, has reduced expression of proteins critical for barrier function, and shows little recovery of the permeability barrier when disrupted. Thus in vivo and in vitro, calcium and 1,25(OH)(2)D interact at multiple levels to regulate epidermal differentiation. (C) 2004 Elsevier Ltd. All rights reserved.