Herrmann G, Wlaschek M, Lange T S, Prenzel K, Goerz G, Scharffetter-Kochanek K
Department of Dermatology, Heinrich-Heine-University of Düsseldorf, Germany.
Exp Dermatol. 1993 Mar;2(2):92-7. doi: 10.1111/j.1600-0625.1993.tb00015.x.
UVA irradiation leads to photoaging including clinical features such as wrinkle formation, reduced recoil capacity and blister formation of the skin. Besides synthesis of the extracellular matrix, its regulated degradation by various matrix-metalloproteinases (MMPs) determines the amount and the composition of the extracellular matrix within the dermis and the basement membrane of the dermo-epidermal junction. In this study we therefore ascertained whether UV irradiation could modulate the synthesis of MMPs with substrate specificities for dermal (collagen I, III, V) and basement membrane compounds (collagen IV, VII, proteoglycans, laminin) and whether synthesis of the counteracting tissue inhibitor of metalloproteinases (TIMP-1) was also affected. Following UVA irradiation specific mRNAs of MMPs 1, 2 and 3 were induced concomitantly up to 5-fold compared to mock irradiated controls. In contrast, TIMP-1 mRNA levels remained unaltered. Immunoprecipitation indicated that after UVA irradiation synthesis and secretion of MMPs 1, 2 and 3 into the supernatant increased. Taken together, our data show that UVA irradiation coordinately induced MMPs 1, 2 and 3 implying similar mechanisms in their regulatory pathways, while TIMP-1 synthesis was not altered. Hence, unbalanced synthesis of MMPs potentially contributes to the dissolution of dermal and basement membrane compounds finally leading to blister formation and cutaneous photoaging.
紫外线A（UVA）照射会导致皮肤光老化，出现诸如皱纹形成、皮肤回缩能力降低以及水疱形成等临床特征。除了细胞外基质的合成外，各种基质金属蛋白酶（MMPs）对其进行的调控性降解决定了真皮内以及真皮-表皮连接处基底膜中细胞外基质的数量和组成。因此，在本研究中，我们确定了紫外线照射是否能够调节对真皮（I型、III型、V型胶原蛋白）和基底膜成分（IV型、VII型胶原蛋白、蛋白聚糖、层粘连蛋白）具有底物特异性的基质金属蛋白酶的合成，以及金属蛋白酶组织抑制剂（TIMP-1）的合成是否也受到影响。与未照射的对照组相比，紫外线A照射后，基质金属蛋白酶1、2和3的特定信使核糖核酸（mRNAs）同时被诱导增加了5倍。相比之下，TIMP-1信使核糖核酸水平保持不变。免疫沉淀表明，紫外线A照射后，基质金属蛋白酶1、2和3的合成及分泌到上清液中的量增加。综上所述，我们的数据表明，紫外线A照射协同诱导了基质金属蛋白酶1、2和3，这意味着它们的调控途径存在相似机制，而TIMP-1的合成未发生改变。因此，基质金属蛋白酶的不平衡合成可能会导致真皮和基底膜成分的溶解，最终导致水疱形成和皮肤光老化。
