Rays and arrays: the transcriptional program in the response of human epidermal keratinocytes to UVB illumination
Rays and arrays: the transcriptional program in the response of human epidermal keratinocytes to UVB illumination
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DOI：
10.1096/fj.01-0172fje
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发表时间：
2001-09-01
期刊：
影响因子：
4.8
通讯作者：
Blumenberg, M
中科院分区：
文献类型：
--
作者：
Li, DL;Turi, TG;Blumenberg, M
表皮是我们抵御紫外线 (UV) 的第一道防线，承受着大部分光损伤，导致皮肤变薄、起皱、角化和恶性肿瘤。假设皮肤具有保护自身和生物体免受紫外线伤害的特定机制，我们使用 DNA 阵列来跟踪表皮角质形成细胞中紫外线引起的基因表达变化。在检查的 6,800 个基因中，紫外线调节了至少 198 个基因的表达。可以区分基因表达的三波变化：光照后 0.5-2、4-8 和 16-24 小时。第一个包含转录因子、信号转导和细胞骨架蛋白，它们将细胞表型从正常、快速生长的细胞改变为激活的、暂停的细胞。第二种包含分泌的生长因子、细胞因子和趋化因子；角质形成细胞改变了自身的生理机能，向周围组织发出紫外线损伤的警报。第三波包含角质化包膜的成分，因为角质形成细胞增强了表皮保护层，同时最终分化和死亡，消除了致癌威胁。紫外线还诱导提供额外能量的线粒体蛋白的表达，以及合成 DNA 修复原材料的酶。使用新型皮肤器官培养模型，我们证明在角质形成细胞培养物中检测到的紫外线诱导的变化也发生在人体内表皮中。
The epidermis, our first line of defense from ultraviolet (UV) light, bears the majority of photodamage, which results in skin thinning, wrinkling, keratosis, and malignancy. Hypothesizing that skin has specific mechanisms to protect itself and the organism from UV damage, we used DNA arrays to follow UV-caused gene expression changes in epidermal keratinocytes. Of the 6,800 genes examined, UV regulates the expression of at least 198. Three waves of changes in gene expression can be distinguished, 0.5-2, 4-8, and 16-24 h after illumination. The first contains transcription factors, signal transducing, and cytoskeletal proteins that change cell phenotype from a normal, fast-growing cell to an activated, paused cell. The second contains secreted growth factors, cytokines, and chemokines; keratinocytes, having changed their own physiology, alert the surrounding tissues to the UV damage. The third wave contains components of the cornified envelope, as keratinocytes enhance the epidermal protective covering and, simultaneously, terminally differentiate and die, removing a carcinogenic threat. UV also induces the expression of mitochondrial proteins that provide additional energy, and the enzymes that synthesize raw materials for DNA repair. Using a novel skin organ culture model, we demonstrated that the UV-induced changes detected in keratinocyte cultures also occur in human epidermis in vivo.