Skarmoutsou Evangelia, Trovato Chiara, Granata Mariagrazia, Rossi Giulio A, Mosca Ambra, Longo Valentina, Gangemi Pietro, Pettinato Maurizio, D'Amico Fabio, Mazzarino Maria Clorinda
Department of Biomedical and Biotechnological Sciences, University of Catania, via Androne 83, 95124, Catania, Italy.
Unità Operativa Complessa di Dermatologia, Azienda Ospedaliera Universitaria Policlinico-Vittorio Emanuele, Catania, Italy.
Arch Dermatol Res. 2015 Dec;307(10):863-73. doi: 10.1007/s00403-015-1594-7. Epub 2015 Aug 30.
Psoriasis is a chronic inflammatory skin disease, characterized by hyperproliferation of keratinocytes and by skin infiltration of activated T cells. To date, the pathophysiology of psoriasis has not yet been fully elucidated. The Notch pathway plays a determinant role in cell fate determination, proliferation, differentiation, immune cell development and function. Many biological agents, used in the treatment of psoriasis, include TFN-α inhibitors, such as etanercept, adalimumab, and anti IL-12/IL-23 p40 antibody, such as ustekinumab. This study aimed to determine mRNA expression levels by real-time RT-PCR, and protein expression levels, analysed by Western blot and immunohistochemistry, of some components of the Notch pathway, such as NOTCH1, NOTCH2, JAGGED1, and HES1 after biological treatments in psoriatic patients. mRNA and protein levels of NOTCH1, NOTCH2, JAGGED1 and HES1 were upregulated in skin samples from untreated psoriatic patients compared with normal controls. Biological therapy showed to downregulate differently the protein expression levels of the molecules under study. Our study suggests that Notch pathway components might be a potential therapeutic target against psoriasis.
银屑病是一种慢性炎症性皮肤病，其特征为角质形成细胞过度增殖以及活化T细胞浸润皮肤。迄今为止，银屑病的病理生理学尚未完全阐明。Notch信号通路在细胞命运决定、增殖、分化、免疫细胞发育及功能方面起决定性作用。许多用于治疗银屑病的生物制剂包括TNF-α抑制剂，如依那西普、阿达木单抗，以及抗IL-12/IL-23 p40抗体，如乌司奴单抗。本研究旨在通过实时逆转录聚合酶链反应（RT-PCR）确定银屑病患者经生物治疗后Notch信号通路某些成分（如NOTCH1、NOTCH2、JAGGED1和HES1）的mRNA表达水平，并通过蛋白质印迹法和免疫组织化学分析其蛋白质表达水平。与正常对照相比，未经治疗的银屑病患者皮肤样本中NOTCH1、NOTCH2、JAGGED1和HES1的mRNA和蛋白质水平上调。生物治疗显示对所研究分子的蛋白质表达水平有不同程度的下调。我们的研究表明，Notch信号通路成分可能是治疗银屑病的潜在靶点。
