OPPEN COSMETICS CO., LTD., Kusatsu-shi, Shiga, Japan.
School of Bioscience and Biotechnology, Tokyo University of Technology, Hachiouji, Tokyo, Japan.
Exp Dermatol. 2018 May;27(5):520-525. doi: 10.1111/exd.13522. Epub 2018 Apr 10.
Photoaging of the skin is marked by obvious wrinkles and mainly depends on degradation of the extracellular matrix (ECM) in the dermis. Matrix metalloproteinase (MMP)-1 is one of the most important factors involved in degradation of the ECM; however, its mechanism of activation is not fully understood. It has been thought that MMP-1 is expressed by dermal fibroblasts as an inactive precursor protein that is activated by proteinases produced by keratinocytes in the epidermis. In this study, we constructed a 3D model of the dermis using collagen-embedded fibroblasts with or without ultraviolet (UV)-A exposure to mimic photoaging in the dermis. Collagen lattices embedded with UV-A-irradiated fibroblasts miniaturized and collagen was degraded to a greater extent than collagen lattices embedded with non-irradiated fibroblasts. The results demonstrate that fibroblasts in this 3D model express activated MMP-1 in the absence of keratinocytes. Moreover, the results confirm that activation of MMP-1 depends on increased plasmin activity in this model and lattice miniaturization was inhibited by the plasmin inhibitor tranexamic acid. Our results suggest that plasmin acts as an activator of MMP-1 and the inhibition of plasmin prevents collagen degradation.
皮肤的光老化表现为明显的皱纹，主要取决于真皮中细胞外基质（ECM）的降解。基质金属蛋白酶（MMP）-1是参与 ECM 降解的最重要因素之一，但其激活机制尚不完全清楚。人们认为 MMP-1 由真皮成纤维细胞作为无活性的前体蛋白表达，该蛋白被表皮角质形成细胞产生的蛋白酶激活。在这项研究中，我们使用嵌入有或没有紫外线（UV）-A 暴露的成纤维细胞构建了真皮的 3D 模型，以模拟真皮中的光老化。与嵌入未辐照成纤维细胞的胶原格子相比，嵌入经 UV-A 辐照的成纤维细胞的胶原格子会缩小，胶原降解程度更大。结果表明，在没有角质形成细胞的情况下，该 3D 模型中的成纤维细胞表达激活的 MMP-1。此外，结果证实 MMP-1 的激活取决于该模型中纤溶酶活性的增加，并且纤溶酶抑制剂氨甲环酸抑制格子缩小。我们的结果表明，纤溶酶作为 MMP-1 的激活剂发挥作用，纤溶酶的抑制可防止胶原降解。
