The First People's Hospital of Taicang, Jiangsu, China.
Department of Key Laboratory, The Second People's Hospital of Changshu, The Affiliated Changshu Hospital of Xuzhou Medical University, Jiangsu, China.
Int J Rheum Dis. 2020 Oct;23(10):1318-1327. doi: 10.1111/1756-185X.13930. Epub 2020 Aug 4.
Rheumatoid arthritis (RA) is an inflammatory disease, which seriously affects human joints. This study aimed to detect the changes in the expression of long non-coding RNA growth arrest-specific transcript 5 (GAS5) in peripheral blood mononuclear cells (PBMCs) derived from patients with RA and healthy controls (HC), as well as analyze the correlation between GAS5 and clinical indicators of RA. Also, the role and mechanism of GAS5 in regulating the AMP-activated protein kinase (AMPK) pathway in RA was further assessed.
The PBMCs were isolated from the RA patients. Next, GAS5 expression was detected in RA PBMCs by quantitative real-time polymerase chain reaction, and its diagnostic value on RA was determined by receiver operating characteristic curves (ROC). The levels of interleukin (IL)-6 and IL-17 were detected via enzyme-linked immunosorbent assay. The expressions of total and phosphorylated AMPK as well as p38MAPK were determined with Western blot.
GAS5 was down-regulated in RA PBMCs, and consequently serves as a potential diagnostic marker for RA (sensitivity, 90%; specificity, 80%; area under the curve, 0.89). Further, GAS5 negatively regulated erythrocyte sedimentation rate, C-reactive protein, Disease Activity Score of 28 joints and antibodies against cyclic citrullinated peptide, as well as the IL-6 and IL-17 levels of RA PBMCs. Similarly, GAS5 was observed to activate the AMPK pathway.
GAS5 activated the AMPK pathway, while it negatively regulated the expression of cytokines IL-6 and IL-17.
类风湿关节炎（RA）是一种炎症性疾病，严重影响人类关节。本研究旨在检测 RA 患者和健康对照者（HC）外周血单个核细胞（PBMC）中长链非编码 RNA 生长停滞特异性转录物 5（GAS5）表达的变化，并分析 GAS5 与 RA 临床指标的相关性。此外，还进一步评估了 GAS5 在调节 RA 中 AMP 激活蛋白激酶（AMPK）通路中的作用和机制。
从 RA 患者中分离 PBMC。然后，通过实时定量聚合酶链反应检测 RA PBMC 中的 GAS5 表达，并通过接收者操作特征曲线（ROC）确定其对 RA 的诊断价值。通过酶联免疫吸附试验检测白细胞介素（IL）-6 和 IL-17 的水平。用 Western blot 测定总和磷酸化 AMPK 以及 p38MAPK 的表达。
GAS5 在 RA PBMC 中下调，可作为 RA 的潜在诊断标志物（灵敏度 90%，特异性 80%，曲线下面积 0.89）。此外，GAS5 负调控红细胞沉降率、C 反应蛋白、28 个关节疾病活动评分和抗环瓜氨酸肽抗体，以及 RA PBMC 中 IL-6 和 IL-17 的水平。同样，观察到 GAS5 激活 AMPK 通路。
GAS5 激活 AMPK 通路，同时负调控细胞因子 IL-6 和 IL-17 的表达。
