Grabarek Beniamin, Wcislo-Dziadecka Dominika, Gola Joanna, Kruszniewska-Rajs Celina, Brzezinska-Wcislo Ligia, Zmarzly Nikola, Mazurek Urszula
Department of Molecular Biology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, ul. Jedności 8, 41-206 Sosnowiec, Poland.
Department of Skin Structural Studies, Chair of Cosmetology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, ul. Kasztanowa 3, 41-200 Sosnowiec, Poland.
Curr Pharm Biotechnol. 2018;19(7):556-565. doi: 10.2174/1389201019666180730094046.
The aim of this study was to evaluate the influence of adalimumab on the expression pattern of genes associated with JAK/STAT signaling pathway in Normal Human Dermal Fibroblast (NHDF) cells stimulated with 8 µg/ml of adalimumab and the identification of miRNAs regulating these genes' expression.
NHDFs were cultured with or without the presence of adalimumab for 2, 8, and 24h. The microarray technology was used to determine expression profile of mRNAs and miRNAs.
Out of 22283 ID mRNA, 37 are associated with the JAK/STAT signaling pathway. It can be observed that 18 mRNAs differentiate NHDFs cultures with adalimumab from control. The analysis of miRNAs showed that, among 1105 ID miRNAs, 20 miRNAs are differentiating in cells treated with adalimumab for 2h, 9 miRNAs after 8h, and only 3 miRNAs after 24h.
It can be observed that miRNAs play an extremely important role in the regulation of the expression of genes associated with JAK/STAT signaling pathway. The results of this study show the possibility of using changes in mRNAs and miRNAs profile expression, as complementary molecular markers of adalimumab treatment effectiveness.
本研究旨在评估阿达木单抗对用8μg/ml阿达木单抗刺激的正常人皮肤成纤维细胞（NHDF）中与JAK/STAT信号通路相关基因表达模式的影响，并鉴定调节这些基因表达的微小RNA（miRNA）。
NHDF在有或无阿达木单抗存在的情况下培养2、8和24小时。使用微阵列技术确定mRNA和miRNA的表达谱。
在22283个ID mRNA中，37个与JAK/STAT信号通路相关。可以观察到，18个mRNA可区分用阿达木单抗处理的NHDF培养物与对照。对miRNA的分析表明，在1105个ID miRNA中，20个miRNA在用阿达木单抗处理2小时的细胞中存在差异，8小时后有9个miRNA存在差异，24小时后只有3个miRNA存在差异。
可以观察到miRNA在调节与JAK/STAT信号通路相关基因的表达中发挥着极其重要的作用。本研究结果表明，利用mRNA和miRNA谱表达的变化作为阿达木单抗治疗效果的补充分子标志物具有可能性。
