Dong Kelly K, Damaghi Niusha, Picart Stephanie D, Markova Nelli G, Obayashi Kei, Okano Yuri, Masaki Hitoshi, Grether-Beck Susanne, Krutmann Jean, Smiles Kenneth A, Yarosh Daniel B
AGI Dermatics, Freeport, New York, USA.
Exp Dermatol. 2008 Dec;17(12):1037-44. doi: 10.1111/j.1600-0625.2008.00747.x. Epub 2008 May 3.
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.
胶原蛋白的破坏是光老化的一个标志。负责消化I型胶原蛋白的主要酶——基质金属蛋白酶-1（MMP-1），是由阳光照射诱导产生的。为了研究这种诱导作用的分子触发因素，对人类皮肤进行紫外线B（UVB）照射，并使用脂质体包裹的DNA修复酶进行处理。光解酶介导的表皮UV损伤的DNA修复与皮肤表皮和真皮层中MMP-1 mRNA和蛋白表达的降低相关。当用UVB照射人类表皮角质形成细胞，并将其培养基转移至未照射的人类真皮成纤维细胞时，研究了表皮细胞在成纤维细胞中MMP-1诱导过程中的作用。将照射过的角质形成细胞的培养基转移至未照射的成纤维细胞中，会增强MMP-1 mRNA和蛋白的表达。因此，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蛋白的破坏，这些介质向成纤维细胞发出信号，促使其释放MMP-1。在将培养基转移至成纤维细胞之前，用DNA修复酶T4内切核酸酶V或UV内切核酸酶处理角质形成细胞，MMP-1的诱导作用会降低。这意味着，UVB将其大部分能量沉积在表皮角质形成细胞的染色质上，在真皮上层沉积的能量较少，在光老化中起重要作用。角质形成细胞中的DNA损伤启动了MMP-1释放的信号之一，增强DNA修复可以降低人类皮肤细胞和组织中MMP-1的表达。
