Regulation of human epidermal keratinocyte differentiation by the vitamin D receptor and its coactivators DRIP205, SRC2, and SRC3
Regulation of human epidermal keratinocyte differentiation by the vitamin D receptor and its coactivators DRIP205, SRC2, and SRC3
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DOI：
10.1038/sj.jid.5700624
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发表时间：
2007-04-01
影响因子：
6.5
通讯作者：
Bikle, Daniel D.
中科院分区：
文献类型：
--
作者：
Hawker, Nathaniel P.;Pennypacker, Sally D.;Bikle, Daniel D.
长期以来，已知维生素D的活性代谢物1，25二羟基维生素D-3通过与维生素D受体（VDR）的相互作用刺激表皮角质形成细胞的分化并抑制增殖。VDR通过DNA中的维生素D反应元件和有助于启动转录的特异性共激活蛋白的协同结合发挥作用。最近观察到，在角质形成细胞分化过程中，VDR结合两种主要的辅激活因子复合物，DRIP（VDR相互作用蛋白）和SRC（类固醇受体辅激活因子）。为了确定VDR及其辅激活因子在介导角质形成细胞分化中的作用，我们开发了一种腺病毒系统来敲低或在VDR的情况下过表达这些基因。为了研究角质形成细胞发育的所有阶段，我们采用了一种先进的分化正常人角质形成细胞培养系统，该系统产生与正常皮肤相似的多层表型。这些研究表明，VDR、DRIP和SRC都是促进早期和晚期角质形成细胞分化所必需的。此外，所测定的每个个体分化标志物对于调节其表达的共激活因子具有不同的特异性。
It has long been known that the active metabolite of vitamin D, 1,25 dihydroxyvitamin D-3, stimulates differentiation and inhibits proliferation in epidermal keratinocytes through interaction with the vitamin D receptor (VDR). VDR functions through the coordinate binding of vitamin D response elements in the DNA and specific coactivator proteins which help to initiate transcription. It was recently observed that VDR binds to two major coactivator complexes, DRIP (VDR-interacting protein) and SRC (steroid receptor coactivator), during keratinocyte differentiation. To determine the role of VDR and its coactivators in mediating keratinocyte differentiation, we developed an adenoviral system to knock down, or in the case of VDR, overexpress these genes. In order to study all stages of keratinocyte development, we employed an advanced differentiated normal human keratinocyte culture system that produces a multilayer phenotype similar to that of normal skin. These studies have shown that VDR, DRIP, and SRC are all required for promotion of both early and late keratinocyte differentiation. Additionally, each individual differentiation marker that was assayed has a different specificity for the coactivators that regulate its expression.