Matsui Mio, Tanaka Kosuke, Higashiguchi Naoki, Okawa Hisato, Yamada Yoichi, Tanaka Ken, Taira Soichiro, Aoyama Tomoko, Takanishi Misaki, Natsume Chika, Takakura Yuuki, Fujita Norihisa, Hashimoto Takeshi, Fujita Takashi
Molecular Toxicology Lab., Ritsumeikan University, Shiga, Japan.
Infection Control Lab., Ritsumeikan University, Shiga, Japan.
J Pharmacol Sci. 2016 Sep;132(1):55-64. doi: 10.1016/j.jphs.2016.08.004. Epub 2016 Aug 12.
Mild exposure to ultraviolet (UV) radiation is also harmful and hazardous to the skin and often causes a photosensitivity disorder accompanied by sunburn. To understand the action of UV on the skin we performed a microarray analysis to isolate UV-sensitive genes. We show here that UV irradiation promoted sunburn and downregulated filaggrin (Flg); fucoxanthin (FX) exerted a protective effect. In vitro analysis showed that UV irradiation of human dermal fibroblasts caused production of intracellular reactive oxygen species (ROS) without cellular toxicity. ROS production was diminished by N-acetylcysteine (NAC) or FX, but not by retinoic acid (RA). In vivo analysis showed that UV irradiation caused sunburn and Flg downregulation, and that FX, but not NAC, RA or clobetasol, exerted a protective effect. FX stimulated Flg promoter activity in a concentration-dependent manner. Flg promoter deletion and chromatin immunoprecipitation analysis showed that caudal type homeo box transcription factor 1 (Cdx1) was a key factor for Flg induction. Cdx1 was also downregulated in UV-exposed skin. Therefore, our data suggested that the protective effects of FX against UV-induced sunburn might be exerted by promotion of skin barrier formation through induction of Flg, unrelated to quenching of ROS or an RA-like action.
轻度暴露于紫外线(UV)辐射对皮肤也是有害的,并且常常会引发伴有晒伤的光敏性疾病。为了了解紫外线对皮肤的作用,我们进行了微阵列分析以分离紫外线敏感基因。我们在此表明,紫外线照射会加剧晒伤并下调丝聚合蛋白(Flg);岩藻黄质(FX)具有保护作用。体外分析表明,紫外线照射人皮肤成纤维细胞会导致细胞内活性氧(ROS)的产生,但无细胞毒性。N-乙酰半胱氨酸(NAC)或FX可减少ROS的产生,但视黄酸(RA)则不能。体内分析表明,紫外线照射会导致晒伤和Flg下调,并且FX具有保护作用,而NAC、RA或丙酸氯倍他索则没有。FX以浓度依赖的方式刺激Flg启动子活性。Flg启动子缺失和染色质免疫沉淀分析表明,尾型同源盒转录因子1(Cdx1)是Flg诱导的关键因子。在紫外线照射的皮肤中Cdx1也会下调。因此,我们的数据表明,FX对紫外线诱导的晒伤的保护作用可能是通过诱导Flg促进皮肤屏障形成来实现的,这与ROS的淬灭或类RA作用无关。