Pathophysiology of premature skin aging induced by ultraviolet light
Pathophysiology of premature skin aging induced by ultraviolet light
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DOI：
10.1056/nejm199711133372003
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发表时间：
1997-11-13
影响因子：
158.5
通讯作者：
Voorhees, JJ
中科院分区：
文献类型：
--
作者：
Fisher, GJ;Wang, ZQ;Voorhees, JJ
研究背景长期暴露于阳光中的紫外线照射会导致皮肤过早老化（光老化），其特征部分表现为皱纹、色素沉着改变和肤色丧失。光老化的皮肤显示结缔组织的胶原性细胞外基质的显著改变。我们研究了基质降解金属蛋白酶，一个家庭的蛋白水解酶的作用，作为介质的胶原蛋白损伤的photoageing.Methods我们研究了59个白人（33名男性和26名女性，年龄范围从21岁至58岁）轻至中度的皮肤色素沉着，没有人有当前或以前的皮肤疾病。只有一些参与者被纳入每项研究。我们在标准条件下用荧光紫外线照射他们的皮肤，并通过角膜刀或打孔活检从照射和非照射区域获得皮肤样本。在一些研究中，在紫外线照射前48小时，将维甲酸及其赋形剂施用于封闭的皮肤。基质金属蛋白酶的表达通过原位杂交、免疫组织化学和原位酶谱法测定。辐射诱导的皮肤胶原蛋白的降解通过可溶性交联端肽的放射免疫测定来测量。结果单次紫外线照射可使皮肤结缔组织和外层皮肤中胶原酶、92 kd明胶酶和基质溶解素3种基质金属蛋白酶的表达增加，与未照射皮肤相比，其表达量明显增加。内源性I型胶原纤维的降解增加了58%，在照射皮肤，与非照射皮肤相比。胶原酶和明胶酶活性保持最大升高（分别为4.4和2.3倍）持续7天，接受四次紫外线照射，每隔两天进行一次，与基线水平相比，用维甲酸预处理皮肤（全反式维甲酸）抑制基质金属蛋白酶蛋白和活性的诱导（70%至80%）在结缔组织和受照射皮肤的外层。紫外线照射也诱导基质金属蛋白酶组织抑制剂-1，调节酶。诱导的抑制剂是不受影响的维甲酸。结论多次暴露于紫外线照射导致基质金属蛋白酶的持续升高，降解皮肤胶原蛋白，可能有助于光老化。局部用维甲酸治疗抑制辐射诱导的基质金属蛋白酶，但不抑制其内源性抑制剂。(C)1997年，马萨诸塞州医学会。
Background Long-term exposure to ultraviolet irradiation from sunlight causes premature skin aging (photoaging), characterized in part by wrinkles, altered pigmentation, and loss of skin tone. Photoaged skin displays prominent alterations in the collagenous extracellular matrix of connective tissue. We investigated the role of matrix-degrading metalloproteinases, a family of proteolytic enzymes, as mediators of collagen damage in photoaging.Methods We studied 59 whites (33 men and 26 women, ranging in age from 21 to 58 years) with light-to-moderate skin pigmentation, none of whom had current or prior skin disease. Only some of the participants were included in each of the studies. We irradiated their buttock skin with fluorescent ultraviolet lights under standard conditions and obtained skin samples from irradiated and nonirradiated areas by keratome or punch biopsy. in some studies, tretinoin and its vehicle were applied to skin under occlusion 48 hours before ultraviolet irradiation. The expression of matrix metalloproteinases was determined by in situ hybridization, immunohistology, and in situ zymography. Irradiation-induced degradation of skin collagen was measured by radioimmunoassay of soluble cross-linked telopeptides. The protein lever of tissue inhibitor of matrix metalloproteinases type 1 was determined by Western blot analysis.Results A single exposure to ultraviolet irradiation increased the expression of three matrix metalloproteinases - collagenase, a 92-kd gelatinase, and stromelysin - in skin connective tissue and outer skin layers, as compared with nonirradiated skin. The degradation of endogenous type I collagen fibrils was increased by 58 percent in irradiated skin, as compared with nonirradiated skin. Collagenase and gelatinase activity remained maximally elevated (4.4 and 2.3 times, respectively) for seven days with four exposures to ultraviolet irradiation, delivered at two-day intervals, as compared with base-line levels, Pretreatment of skin with tretinoin (all-trans-retinoic acid) inhibited the induction of matrix metalloproteinase proteins and activity (by 70 to 80 percent) in both connective tissue and outer layers of irradiated skin. Ultraviolet irradiation also induced tissue inhibitor of matrix metalloproteinases-1, which regulates the enzyme. Induction of the inhibitor was not affected by tretinoin.Conclusions Multiple exposures to ultraviolet irradiation lead to sustained elevations of matrix metalloproteinases that degrade skin collagen and may contribute to photoaging. Treatment with topical tretinoin inhibits irradiation-induced matrix metalloproteinases but not their endogenous inhibitor. (C) 1997, Massachusetts Medical Society.