Department of Dermatology, Venereology and Oncodermatology, Medical School, University of Pécs, H-7632 Pecs, Hungary.
Int J Mol Sci. 2021 Dec 23;23(1):121. doi: 10.3390/ijms23010121.
Psoriasis is a systemic inflammatory skin disorder that can be associated with sleep disturbance and negatively influence the daily rhythm. The link between the pathomechanism of psoriasis and the circadian rhythm has been suggested by several previous studies. However, there are insufficient data on altered clock mechanisms in psoriasis to prove these theories. Therefore, we investigated the expression of the core clock genes in human psoriatic lesional and non-lesional skin and in human adult low calcium temperature (HaCaT) keratinocytes after stimulation with pro-inflammatory cytokines. Furthermore, we examined the clock proteins in skin biopsies from psoriatic patients by immunohistochemistry. We found that the clock gene transcripts were elevated in psoriatic lesions, especially in non-lesional psoriatic areas, except for , which was consistently downregulated in the psoriatic samples. In addition, the REV-ERBα protein showed a different epidermal distribution in non-lesional skin than in healthy skin. In cytokine-treated HaCaT cells, changes in the amplitude of the , , and mRNA oscillation were observed, especially after TNFα stimulation. In conclusion, in our study a perturbation of clock gene transcripts was observed in uninvolved and lesional psoriatic areas compared to healthy skin. These alterations may serve as therapeutic targets and facilitate the development of chronotherapeutic strategies in the future.
银屑病是一种系统性炎症性皮肤疾病，可与睡眠障碍相关，并对日常节律产生负面影响。几项先前的研究提示了银屑病的发病机制与昼夜节律之间的联系。然而，银屑病时钟机制改变的相关数据不足，无法证明这些理论。因此，我们研究了在受到促炎细胞因子刺激后，人银屑病皮损和非皮损皮肤以及人成纤维细胞角质形成细胞（HaCaT）中的核心时钟基因的表达。此外，我们通过免疫组织化学检查了银屑病患者皮肤活检中的时钟蛋白。我们发现，时钟基因转录本在银屑病皮损中升高，尤其是在非皮损银屑病区域，但 除外，其在银屑病样本中持续下调。此外，REV-ERBα 蛋白在非皮损皮肤中的表皮分布与健康皮肤不同。在细胞因子处理的 HaCaT 细胞中，观察到 、 、 和 的 mRNA 振荡幅度发生变化，尤其是在 TNFα 刺激后。总之，与健康皮肤相比，我们的研究观察到未受累和受累银屑病区域的时钟基因转录本受到干扰。这些改变可能作为治疗靶点，并有助于未来制定时间治疗策略。
