c-Jun-dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoic acid
c-Jun-dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoic acid
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DOI：
10.1172/jci9362
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发表时间：
2000-09-01
影响因子：
15.9
通讯作者：
Voorhees, JJ
中科院分区：
文献类型：
--
作者：
Fisher, GJ;Datta, S;Voorhees, JJ
反复暴露于太阳紫外线（UV）照射后皮肤的老化外观主要源于对皮肤结缔组织的损伤，皮肤结缔组织主要由I型和III型胶原组成。我们在这里报告，一个单一的暴露于紫外线照射导致显着损失的前胶原合成在人体皮肤。I型和III型前胶原的表达在单次UV暴露后24小时内显著降低，即使在仅引起最小皮肤发红的UV剂量下也是如此。每日紫外线暴露超过4天，导致I型和III型前胶原蛋白水平在最终紫外线暴露后持续降低至少24小时。UV抑制I型前胶原合成部分由c-Jun介导，c-Jun由IV照射诱导并干扰前胶原转录。用全反式维甲酸在体内预处理人皮肤抑制c-Jun的UV诱导并保护皮肤免受前胶原合成的损失。我们以前曾报道，紫外线照射诱导基质降解金属蛋白酶在人体皮肤和皮肤预处理全反式维甲酸抑制这种诱导。因此，紫外线照射通过同时抑制前胶原合成和刺激胶原分解来损伤人皮肤结缔组织。全反式视黄酸可以防止这两种有害作用，从而延缓皮肤过早老化。
The aged appearance of skin following repeated exposure to solar ultraviolet (UV) irradiation stems largely from damage to cutaneous connective tissue, which is composed primarily of type I and type III collagens. We report here that a single exposure to UV irradiation causes significant loss of procollagen synthesis in human skin. Expression of type I and type III procollagens is substantially reduced within 24 hours after a single UV exposure, even at UV doses that cause only minimal skin reddening. Daily UV exposures over 4 days result in sustained reductions of both type I and type III procollagen protein levels for at least 24 hours after the final UV exposure. UV inhibition of type I procollagen synthesis is mediated in part by c-Jun, which is induced by IV irradiation and interferes with procollagen transcription. Pretreatment of human skin in vivo with all-trans retinoic acid inhibits UV induction of c-Jun and protects skin against loss of procollagen synthesis. We have reported previously that UV irradiation induces matrix-degrading metalloproteinases in human skin and that pretreatment of skin with all-trans retinoic acid inhibits this induction. UV irradiation, therefore, damages human skin connective tissue by simultaneously inhibiting procollagen synthesis and stimulating collagen breakdown. All-trans retinoic acid protects against both of these deleterious effects and may thereby retard premature skin aging.