Department of Nutrigenomics and Bromatology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Sosnowiec, Poland.
Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Sosnowiec, Poland.
Curr Pharm Biotechnol. 2023;24(2):330-340. doi: 10.2174/1389201023666220628111644.
MAP kinases are some of the cascades that are specialized in the cell's response to external stimuli. Their impaired functioning can be observed during the course of psoriatic arthritis. Currently, the best-known class of biological drugs is the inhibitors of the proinflammatory cytokine TNF-α, including adalimumab.
The aim of this study was to assess changes in the expression of MAP kinase genes in patients with psoriatic arthritis treated with adalimumab, as well as to determine which of the analyzed transcripts could be used as a diagnostic or therapeutic target.
An analysis was performed on the total RNA extracted from PBMCs of patients with psoriatic arthritis before and after three months of adalimumab therapy as well as from a control group. Changes in the expression of the mitogen-activated protein kinase genes were assessed using the HG-U133A 2.0 oligonucleotide microarray method, while the obtained results were validated using the real-time RT-qPCR method.
Using the oligonucleotide microarray method, 14 genes coded for proteins from the MAPK group were identified with at least a two-fold change of expression in the control group and during adalimumab therapy. Validation of the results confirmed a statistically significant decrease in the transcriptional activity of the MAP2K2 gene in the group of patients three months after the administration of adalimumab relative to the control group.
Adalimumab therapy alters the expression of MAPK-coding genes. The assessment of the number of MAP2K2 mRNA molecules can potentially be used in diagnostic analyses or in monitoring adalimumab therapy.
MAP 激酶是专门参与细胞对外界刺激反应的级联反应之一。在银屑病关节炎的发展过程中，可以观察到其功能受损。目前，最知名的生物药物类别是 TNF-α 促炎细胞因子的抑制剂，包括阿达木单抗。
本研究旨在评估接受阿达木单抗治疗的银屑病关节炎患者 MAP 激酶基因表达的变化，并确定分析的转录本中哪些可以用作诊断或治疗靶点。
对接受阿达木单抗治疗前和治疗后三个月的银屑病关节炎患者的 PBMCs 中提取的总 RNA 进行分析，同时对对照组进行分析。采用 HG-U133A 2.0 寡核苷酸微阵列法评估丝裂原活化蛋白激酶基因的表达变化，同时采用实时 RT-qPCR 法验证所得结果。
使用寡核苷酸微阵列法，在对照组和阿达木单抗治疗期间，确定了至少有两个倍数变化的 MAPK 组编码蛋白的 14 个基因。验证结果证实，与对照组相比，阿达木单抗治疗三个月后患者组 MAP2K2 基因的转录活性显著降低。
阿达木单抗治疗改变了 MAPK 编码基因的表达。评估 MAP2K2 mRNA 分子的数量可能可用于诊断分析或监测阿达木单抗治疗。
