UV-induced DNA damage initiates release of MMP-1 in human skin
UV-induced DNA damage initiates release of MMP-1 in human skin
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DOI：
10.1111/j.1600-0625.2008.00747.x
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发表时间：
2008-12-01
影响因子：
3.6
通讯作者：
Yarosh, Daniel B.
中科院分区：
文献类型：
--
作者：
Dong, Kelly K.;Damaghi, Niusha;Yarosh, Daniel B.
胶原蛋白的破坏是光老化的标志。负责胶原蛋白1消化的主要酶基质金属蛋白酶-1（MMP-1）通过暴露于阳光而被诱导。为了研究这种诱导的分子触发因素，对人类皮肤进行紫外线B（UVB）照射，并用脂质体包裹的DNA修复酶进行处理。光解酶介导的DNA修复表皮紫外线损伤与MMP-1的mRNA和蛋白表达的减少在表皮和真皮的皮肤隔间。MMP-1诱导成纤维细胞中的表皮细胞的作用进行了研究，当人表皮角质形成细胞用UVB照射和他们的媒体被转移到未照射的人真皮成纤维细胞。培养基从照射角质形成细胞转移到未照射的成纤维细胞增强MMP-1 mRNA和蛋白。因此，对表皮角质形成细胞的UV损伤可能通过释放可溶性介质参与真皮中胶原的破坏，所述可溶性介质向成纤维细胞发出信号以释放MMP-1。MMP-1的诱导减少时，角质形成细胞用DNA修复酶T4核酸内切酶V或UV核酸内切酶，然后转移到成纤维细胞的媒体。这意味着UVB在光老化中具有重要作用，UVB将其大部分能量沉积在表皮角质形成细胞的染色质上，并在较小程度上沉积在上层真皮中。角质形成细胞中的DNA损伤启动MMP-1释放的信号之一，并且增强DNA修复可以减少人皮肤细胞和组织中MMP-1的表达。
Destruction of collagen is a hallmark of photoaging. The major enzyme responsible for collagen 1 digestion, matrix metalloproteinase-1 (MMP-1), is induced by exposure to sunlight. To study the molecular trigger for this induction, human skin was ultraviolet-B (UVB)-irradiated and treated with liposome-encapsulated DNA repair enzymes. The photolyase-mediated DNA repair of epidermal UV damage was associated with a reduction of MMP-1 mRNA and protein expression in both the epidermal and dermal compartments of the skin. The role of the epidermal cells in MMP-1 induction in the fibroblasts was examined when human epidermal keratinocytes were irradiated with UVB and their media were transferred to unirradiated human dermal fibroblasts. Transfer of media from irradiated keratinocytes to unirradiated fibroblasts enhanced MMP-1 mRNA and protein. Thus, UV damage to keratinocytes of the epidermis may participate in the destruction of collagen in the dermis by release of soluble mediators that signal fibroblasts to release MMP-1. The MMP-1 induction was reduced when the keratinocytes were treated with DNA repair enzymes T4 endonuclease V or UV endonuclease prior to transfer of the media to fibroblasts. This implies that UVB, which deposits most of its energy on the chromatin of the epidermal keratinocytes and to a lesser extent in the upper dermis, has a significant role in photoaging. DNA damage in the keratinocytes initiates one of the signals for MMP-1 release, and enhancing DNA repair can reduce MMP-1 expression in human skin cells and tissue.