SIGNAL TRANSDUCTION FOR PROLIFERATION AND DIFFERENTIATION IN KERATINOCYTES
SIGNAL TRANSDUCTION FOR PROLIFERATION AND DIFFERENTIATION IN KERATINOCYTES
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DOI：
10.1111/j.1749-6632.1988.tb18806.x
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发表时间：
1988-12-31
影响因子：
5.2
通讯作者：
ROOP, DR
中科院分区：
文献类型：
--
作者：
YUSPA, SH;HENNINGS, H;ROOP, DR
在小鼠和人的表皮中，基底细胞层的钙环境明显低于血清钙，而颗粒细胞层的钙环境却异常高。角质形成细胞培养上清液中细胞外钙离子浓度(CaO)的降低维持基本细胞表型，而血清钙离子浓度则诱导终末分化。用Fura 2和数字成像技术对细胞内钙离子(CaI)的测量表明，CaO的增加使CaI增加10-20倍，并保持在较高的水平。伴随着CaI的升高，磷脂酰肌醇(PI)的代谢增加，以产生肌醇磷酸盐和二酰甘油。PI代谢也受到钙离子载体的刺激，这表明CaI的升高是直接原因。随之而来的二酰甘油和CaI的增加将激活蛋白激酶C，这是一种已知的触发表皮分化的事件。特异性CaO和CaI在体外决定角质形成细胞分化的个体标志物的表达。这些发现可能解释了在活体中钙离子梯度对于维持表皮的调节生长和分化的重要性。
In mouse and human epidermis, the Ca2+ environment of the basal cell layer is substantially below serum Ca2+, while that of the granular cell layer is unusually high. Reduction of extracellular Ca2+ concentration (Cao) in the medium of keratinocyte cultures maintains a basal cell phenotype while serum Ca2+ concentrations induce terminal differentiation. Measurements of intracellular Ca2+(Cai) by the use of Fura 2 and digital imaging technology reveal that Cai increases 10-20-fold in response to an increase in Cao and remains elevated. Concomitant with the rise in Cai is an increase in the metabolism of phosphatidylinositol (PI) to yield inositol phosphates and diacylglycerol. PI metabolism is also stimulated by calcium ionophores suggesting that a rise in Cai is directly responsible. The consequent increase in diacylglycerol and Cai would activate protein kinase C, an event known to trigger epidermal differentiation. Specific Cao and Cai determine the expression of individual markers of keratinocyte differentiation in vitro. These findings may account for the importance of the Ca2+ gradient for maintaining regulated growth and differentiation of the epidermis in vivo.