TRANSCRIPTION OF THE HUMAN LORICRIN GENE INVITRO IS INDUCED BY CALCIUM AND CELL-DENSITY AND SUPPRESSED BY RETINOIC ACID

TRANSCRIPTION OF THE HUMAN LORICRIN GENE INVITRO IS INDUCED BY CALCIUM AND CELL-DENSITY AND SUPPRESSED BY RETINOIC ACID
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DOI:
10.1111/1523-1747.ep12469779
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发表时间:
1991-04-01
影响因子:
6.5
通讯作者:
ROOP, DR
ROOP, DR
中科院分区:
医学1区
文献类型:
--
作者:
HOHL, D;LICHTI, U;ROOP, DR

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我们以前已经表明,兜甲蛋白是一个主要组成部分的皮质细胞被膜(CE)的表达晚在表皮分化的颗粒层的正常皮肤。 在各种条件下培养正常人角质形成细胞,并在不同时间点评估兜甲蛋白mRNA水平。 只有高于0.1mM Ca++的Ca++浓度才允许洛里- crin mRNA的表达。 最大的mRNA水平被发现在0.35 mM Ca++和临界细胞密度似乎是所需的最佳积累兜甲蛋白成绩单。 当同时应用时,10(-7)至10(-9)M的视黄酸(RA)完全阻断Ca++诱导的兜甲蛋白mRNA合成。 此外,RA加入到已经暴露于较高Ca++水平的培养物中,导致在48-72 h内兜甲蛋白mRNA完全丧失。 到目前为止,没有其他成分的CE已被证明是由RA抑制。 然而,类似的模式的表达报告丝聚蛋白,基质蛋白也表达表皮分化后期。 因此,我们比较了兜甲蛋白和聚丝蛋白的mRNA水平,发现它们响应于各种培养条件而平行变化。 这些结果表明,Ca++,细胞密度,RA是至关重要的调节器的兜甲蛋白的表达在体外,兜甲蛋白和聚丝蛋白在表皮中的表达的转录控制密切协调。
We have previously shown that loricrin is a major component of the cornified cell envelope (CE) expressed late in epidermal differentiation in the granular layers of normal skin. Normal human keratinocytes were cultured under various conditions and loricrin mRNA levels were assessed at various time points. Only Ca++ concentrations above 0.1 mM Ca++ were permissive for the expression of lori- crin mRNA. Maximal mRNA levels were found at 0.35 mM Ca++ and a critical cell density appeared to be required for optimal accumulation of loricrin transcripts. Retinoic acid (RA) at 10(-7) to 10(-9) M completely blocked Ca++-induced loricrin mRNA synthesis when applied simultaneously. Furthermore, addition of RA to cultures already exposed to higher Ca++ levels resulted in the complete loss of loricrin mRNA within 48-72 h. So far, no other components of the CE have been shown to be suppressed by RA. However, similar patterns of expression were reported for filaggrin, a matrix protein also expressed late in epidermal differentiation. Therefore, we compared the mRNA levels of loricrin and filaggrin and found them to change in parallel in response to the various culture conditions. These results suggest that Ca++, cell density, and RA are crucial regulators of loricrin expression in vitro and that the transcriptional control of loricrin and filaggrin expression in the epidermis are closely coordinated.