ULTRAVIOLET-RADIATION ACTIVATES THE HUMAN ELASTIN PROMOTER IN TRANSGENIC MICE - A NOVEL IN-VIVO AND IN-VITRO MODEL OF CUTANEOUS PHOTOAGING

ULTRAVIOLET-RADIATION ACTIVATES THE HUMAN ELASTIN PROMOTER IN TRANSGENIC MICE - A NOVEL IN-VIVO AND IN-VITRO MODEL OF CUTANEOUS PHOTOAGING
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DOI:
10.1111/1523-1747.ep12318419
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发表时间:
1995-08-01
影响因子:
6.5
通讯作者:
UITTO, J
UITTO, J
中科院分区:
医学1区
文献类型:
--
作者:
BERNSTEIN, EF;BROWN, DB;UITTO, J

文献摘要

被引文献

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光老化皮肤的主要变化是大量异常弹性物质的沉积,称为日光弹性增生症。在以前的工作中,已经表明太阳弹性增生症伴随着弹性蛋白和纤维蛋白mRNAs的丰富和弹性蛋白启动子活性的上调。以组织特异性和发育调控的方式,利用表达人弹性蛋白启动子的转基因小鼠系,在体内和体外研究了紫外线A辐射和紫外线B辐射对人弹性蛋白启动子活性的影响。用单次剂量的紫外线B辐射(491.4 mJ/cm(2))照射小鼠,启动子活性增加了8.5倍,而用紫外线A辐射(38.2J/cm(2))则增加了1.8倍。此外,体外研究表明,弹性蛋白启动子活性在紫外线B辐射(5.5MJ/cm(2))的响应下增加了30倍以上,而在紫外线A辐射(2.2J/cm(2))的响应下没有测量到变化。这些结果证实了紫外线B辐射在光老化过程中弹性蛋白启动子激活中的作用,并确认紫外线A辐射是一个促成因素。该系统可以作为一个有用的体内和体外模型来研究皮肤光老化,并测试可能防止皮肤光损伤的化合物。
The major alteration in photoaged skin is the deposition of massive amounts of abnormal elastic material, termed solar elastosis. In previous work, it has been shown that solar elastosis is accompanied by increased abundance of elastin and fibrillin mRNAs and upregulation of elastin promoter activity. Using a transgenic mouse line, which expresses the human elastin promoter, linked to a chloramphenicol acetyltransferase reporter gene, in a tissue-specific and developmentally regulated manner, we investigated the effects of ultraviolet A radiation and ultraviolet B radiation on human elastin promoter activity in vivo and in vitro. Irradiation of mice with a single dose of ultraviolet B radiation (491.4 mJ/cm(2)) resulted in an increase up to 8.5-fold in promoter activity, whereas a more modest increase of 1.8-fold was measured with ultraviolet A radiation (38.2 J/cm(2)). In addition, in vitro studies revealed over a thirtyfold increase in elastin promoter activity in response to ultraviolet B radiation (5.5 mJ/cm(2)), whereas no change was measured in response to ultraviolet A radiation (2.2 J/cm(2)). These results confirm the role of ultraviolet B radiation in elastin promoter activation in photoaging, and identify ultraviolet A radiation as a contributing factor. This system should serve as a useful in vivo and in vitro model to study cutaneous photoaging, and for testing compounds that may protect against cutaneous photodamage.