Medical Research, Philadelphia Veterans Administration Medical Center, Philadelphia, Pennsylvania, United States of America.
PLoS One. 2011;6(8):e14830. doi: 10.1371/journal.pone.0014830. Epub 2011 Aug 4.
Ultraviolet (UV) light alters cutaneous structure and function. Prior work has shown loss of dermal hyaluronan after UV-irradiation of human skin, yet UV exposure increases total glycosaminoglycan (GAG) content in mouse models. To more fully describe UV-induced alterations to cutaneous GAG content, we subjected human volunteers to intermediate-term (5 doses/week for 4 weeks) or single-dose UV exposure. Total dermal uronyl-containing GAGs increased substantially with each of these regimens. We found that UV exposure substantially increased dermal content of chondroitin sulfate (CS), but not hyaluronan, heparan sulfate, or dermatan sulfate. UV induced the accumulation of both the 4-sulfated (C4S) and 6-sulfated (C6S) isoforms of CS, but in distinct distributions. Next, we examined several CS proteoglycan core proteins and found a significant accumulation of dermal and endothelial serglycin, but not of decorin or versican, after UV exposure. To examine regulation in vitro, we found that UVB in combination with IL-1α, a cytokine upregulated by UV radiation, induced serglycin mRNA in cultured dermal fibroblasts, but did not induce the chondroitin sulfate synthases. Overall, our data indicate that intermediate-term and single-dose UVB exposure induces specific GAGs and proteoglycan core proteins in human skin in vivo. These molecules have important biologic functions and contribute to the cutaneous response to UV.
紫外线 (UV) 会改变皮肤的结构和功能。先前的研究表明,人类皮肤经 UV 照射后会丧失真皮透明质酸,但 UV 暴露会增加小鼠模型中总的糖胺聚糖 (GAG) 含量。为了更全面地描述 UV 对皮肤 GAG 含量的诱导变化,我们让志愿者接受中期(每周 5 次,共 4 周)或单次 UV 照射。这些方案都会使皮肤总尿苷酸 GAG 含量显著增加。我们发现,UV 照射会显著增加皮肤硫酸软骨素 (CS) 的含量,但不会增加透明质酸、硫酸乙酰肝素或硫酸皮肤素。UV 诱导了 CS 的 4-硫酸化 (C4S) 和 6-硫酸化 (C6S) 两种异构体的积累,但分布不同。接下来,我们检查了几种 CS 蛋白聚糖核心蛋白,发现 UV 暴露后真皮和内皮的神经氨酸聚糖明显积累,但 decorin 和 versican 则没有。为了研究体外调节,我们发现 UVB 联合白细胞介素 1α(一种由 UV 辐射上调的细胞因子),可诱导培养的真皮成纤维细胞中的神经氨酸聚糖 mRNA,但不会诱导硫酸软骨素合成酶。总的来说,我们的数据表明,中期和单次 UVB 暴露会在体内诱导人类皮肤中特定的 GAG 和蛋白聚糖核心蛋白。这些分子具有重要的生物学功能,有助于皮肤对 UV 的反应。