1,25(OH)2D3-modulated calcium induced keratinocyte differentiation.
1,25(OH)2D3-modulated calcium induced keratinocyte differentiation.
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1,25(OH)2D3 调节钙诱导角质形成细胞分化。
DOI：
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发表时间：
1996
影响因子：
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通讯作者：
D. Bikle
中科院分区：
文献类型：
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作者：
D. Bikle
角质形成细胞产生维生素D3，将其代谢成其最具生物活性的形式，1，25-二羟基维生素D3（1，25 [OH] 2D 3），并对它们产生的1，25（OH）2D 3作出反应，增殖减少，分化增加。角质形成细胞的1，25（OH）2D 3产生受到严格控制，并随着细胞分化而变化，在分化的早期阶段增加，然后随着终末分化的开始再次减少。内源性产生或外源性提供的1，25（OH）2D 3与钙协同作用，刺激从增殖的基底细胞向终末分化的角质细胞的转变。参与分化过程的蛋白质的mRNA水平不仅受到钙和1，25（OH）2D 3诱导的基因转录增加的控制，而且还受到随后的钙和1，25（OH）2D 3诱导的mRNA不稳定的控制。1，25（OH）2D 3部分通过诱导磷脂酶C增加细胞内钙，磷脂酶C在被激素激活时将磷酸肌醇二磷酸裂解成两种重要的信号分子肌醇三磷酸和甘油二酯。三磷酸肌醇从细胞内储存中释放细胞内钙，细胞内钙的增加打开了钙进入细胞的非特异性阳离子通道。二酰基甘油和细胞内钙促进蛋白激酶C活性，可进一步增强分化过程。1，25（OH）2D 3的这些作用为1，25（OH）2D 3及其类似物在银屑病中的有效性提供了依据。
Keratinocytes produce vitamin D3, metabolize it to its most biologically active form, 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), and respond to the 1,25(OH)2D3 they produce with a decrease in proliferation and an increase in differentiation. 1,25(OH)2D3 production by keratinocytes is tightly controlled and changes as the cells differentiate, increasing during the early stages of differentiation, then decreasing again as terminal differentiation ensues. The 1,25(OH)2D3 produced endogenously or supplied exogenously acts in concert with calcium to stimulate the transition from a proliferating basal cell to a terminally differentiated corneocyte. The mRNA levels for proteins involved in the differentiation process are controlled not only by calcium- and 1,25(OH)2D3-induced increase in gene transcription, but by subsequent calcium- and 1,25(OH)2D3-induced destabilization of the mRNA after adequate levels of the proteins have been produced. 1,25(OH)2D3 increases intracellular calcium in part by inducing phospholipase C, which when activated by hormones, cleaves phosphoinositol bisphosphate into two important signaling molecules inositol tris phosphate and diacylglycerol. Inositol tris phosphate releases intracellular calcium from intracellular stores, and the increase in intracellular calcium opens up the nonspecific cation channel through which calcium enters the cell. Diacylglycerol and intracellular calcium promote protein kinase C activity that can further enhance the differentiation process. These actions of 1,25(OH)2D3 provide the rationale for the effectiveness of 1,25(OH)2D3 and its analogs in psoriasis.