Uncoupling of the calcium-induced terminal differentiation and the activation of membrane-associated transglutaminase in murine keratinocytes by type-beta transforming growth factor.
Uncoupling of the calcium-induced terminal differentiation and the activation of membrane-associated transglutaminase in murine keratinocytes by type-beta transforming growth factor.
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β型转化生长因子解偶联钙诱导的终末分化和小鼠角质形成细胞中膜相关转谷氨酰胺酶的激活。
DOI：
10.1016/0014-4827(89)90421-7
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发表时间：
1989
影响因子：
3.7
通讯作者：
Zhou,ZL
中科院分区：
文献类型：
--
作者：
Reiss,M;Zhou,ZL
钙是培养的表皮细胞终末分化的重要调节因子。为了探讨细胞增殖活性终止与角化过程的关系，我们研究了培养的小鼠皮肤角质形成细胞(BALB/c MK-1)细胞外钙突然升高(钙开关)所引起的事件的时程。在钙浓度为0.10 mm的无血清和无丝裂原的培养液中，这些细胞表现出密度依赖性的生长停滞，没有发生终末分化。钙开关本身就足以诱导剂量依赖的DNA合成爆发，随后细胞对表皮生长因子的有丝分裂刺激逐渐变得不耐受。在钙离子转换后的前6~10h内用β转化生长因子处理细胞，完全消除了细胞对钙的反应所引起的初始的DNA合成爆发和终末分化。另一方面，钙开关还导致角化所需的膜相关形式的谷氨酰胺转氨酶的活性增加四到五倍，而这种活性不受β转化生长因子的存在的影响。这些观察表明，β型转化生长因子调节钙诱导的末端细胞分裂，而不依赖于角化的表型标志物的诱导，如转谷氨酰胺酶。
Calcium is an important regulator of terminal differentiation of cultured epidermal cells. In order to investigate the relationship between the termination of proliferative activity and the process of keratinization, we studied the time course of events induced by a sudden increase of extracellular calcium (calcium-switch) in cultures of established murine skin keratinocytes (BALB/c MK-1). These cells displayed density-dependent growth arrest without undergoing terminal differentiation in the presence of serum- and mitogen-free medium with a calcium concentration <0.10 mM. The calcium-switch alone was sufficient to induce a dose-dependent burst of DNA synthesis, which was followed by a state in which the cells became progressively refractory to mitogenic stimulation with epidermal growth factor. Treatment of cultures with type β transforming growth factor during the first 6- to 10 h following the calcium-switch completely eliminated the initial burst of DNA synthesis as well as the terminal differentiation in response to calcium. On the other hand, the calcium-switch also caused the induction of a four- to fivefold increase of the activity of the membrane-associated form of transglutaminase that is required for keratinization, which was not affected by the presence of type β transforming growth factor. These observations suggest that type β transforming growth factor regulates the calcium-induced terminal cell division independently of the induction of phenotypic markers of keratinization, such as transglutaminase.