Boonpethkaew Suphagan, Meephansan Jitlada, Jumlongpim Onjira, Charoensuksira Sasin, Tangtanatakul Pattarin, Wongpiyabovorn Jongkonnee, Komine Mayumi
Division of Dermatology, Chulabhorn International College of Medicine, Thammasat University, Rangsit Campus, Pathum Thani, Thailand.
Division of Dermatology, Chulabhorn International College of Medicine, Thammasat University, Rangsit Campus, Pathum Thani, Thailand.
J Dermatol Sci. 2022 Oct;108(1):30-38. doi: 10.1016/j.jdermsci.2022.10.003. Epub 2022 Oct 13.
Peripheral edge (PE) of plaques contains inflammatory molecules and has potential to initiate plaque formation, while the center (CE) of plaques has regression trends.
To elucidate the chronological molecular events by comparing the gene profiles in PE skin to those in CE skin.
Biopsied PE, CE, and uninvolved (UN) skin samples were analyzed by next-generation sequencing. Three groups of differentially expressed genes (DEGs) were analyzed, PE/UN-, CE/UN-, and PE/CE-skin-derived DEGs.
PE skin contained inflammation-priming molecules, such as S100A7 and S100A15, and inflammatory drivers, such as interleukin (IL)-36α. IL-6 signaling was more active in PE than in CE skin. IL-8, S100A7, S100A8, S100A9, and human β-defensin-2 were all regulated with the similar pattern in both areas. However, PE skin created a more active inflammatory network and downstream functions, including chemotaxis and angiogenesis, were more prominent than in CE skin. Conversely, CE skin, where epidermal growth factor and hepatocyte growth factor increased their activity, was found to be more stable.
This is the first RNA-seq-based report to determine the chronological molecular events in plaque formation. In the early phase, inflammation might be initiated through molecules, such as IL-36α, S100A7, and S100A15, as observed in PE skin. The inflammation state in PE skin progresses to the more stable state found in CE skin. In CE skin, the growth factor activities are increased, which might lead to attenuation of initial inflammation and initiation of the regression phase. These molecular events may accelerate research towards developing novel therapies for psoriasis.
斑块的外周边缘（PE）含有炎症分子，具有启动斑块形成的潜力，而斑块中心（CE）则有消退趋势。
通过比较PE皮肤与CE皮肤的基因谱，阐明按时间顺序发生的分子事件。
采用二代测序技术分析活检获取的PE、CE和未受累（UN）皮肤样本。分析三组差异表达基因（DEGs），即PE/UN-、CE/UN-和PE/CE-皮肤来源的DEGs。
PE皮肤含有炎症引发分子，如S100A7和S100A15，以及炎症驱动因子，如白细胞介素（IL）-36α。IL-6信号通路在PE皮肤中比在CE皮肤中更活跃。IL-8、S100A7、S100A8、S100A9和人β-防御素-2在两个区域均以相似模式受到调控。然而，PE皮肤形成了更活跃的炎症网络，包括趋化作用和血管生成在内的下游功能比CE皮肤更显著。相反，发现表皮生长因子和肝细胞生长因子活性增加的CE皮肤更稳定。
这是第一份基于RNA测序确定斑块形成过程中按时间顺序发生的分子事件的报告。在早期阶段，炎症可能通过如IL-36α、S100A7和S100A15等分子引发，如在PE皮肤中观察到的那样。PE皮肤中的炎症状态进展为CE皮肤中发现的更稳定状态。在CE皮肤中，生长因子活性增加，这可能导致初始炎症的减弱和消退期的启动。这些分子事件可能加速银屑病新疗法研发的研究进程。
