College of Pharmacy, Anhui University of Chinese Medicine, Qian Jiang Road 1, Hefei 230012, China; Key Laboratory of Xin'an Medicine, Ministry of Education, Hefei 230012, China.
College of Pharmacy, Anhui University of Chinese Medicine, Qian Jiang Road 1, Hefei 230012, China; Key Laboratory of Xin'an Medicine, Ministry of Education, Hefei 230012, China.
Int Immunopharmacol. 2018 Dec;65:284-294. doi: 10.1016/j.intimp.2018.09.049. Epub 2018 Oct 17.
Geniposide (GE) is an active component isolated from the fruit of Gardenia jasminoides Ellis that has anti-inflammatory and other pharmacological effects; however, the underlying mechanism of GE action has not been elucidated in rheumatoid arthritis (RA). Previous studies have shown that GE plays a therapeutic role in RA via regulation of the integrin beta 1 (Itgβ1)-mediated Ras-Erk1/2 signalling pathway. However, the specific mechanism of GE action on Itgβ1 has not been clarified. Recent evidence indicates that microRNAs (miRNAs) are involved in the development of RA. In this study, we developed a miRNA-124a-based synoviocyte repair strategy. We demonstrated that miRNA-124a can directly inhibit the expression of the Itgβ1 gene and decrease TNF-α-stimulated cell proliferation in vitro. MH7A cells were obtained from the patient with RA and treated with GE in the presence of TNF-α (10 ng/mL). Additionally, we demonstrated that the expression of miRNA-124a can be regulated by GE. GE upregulated the expression of miRNA-124a and decreased the expression of Itgβ1 at the mRNA and protein levels. The results of the present study are the first to suggest that GE inhibits TNF-α-stimulated cell proliferation and blocks the activation of the Ras-Erk1/2 pathway via the upregulation of miRNA-124a expression. Our study elucidates the role of miRNA-124a as a protected miRNA in RA and may provide a novel strategy for the diagnosis and treatment of RA in the future.
栀子苷（GE）是从栀子果实中分离得到的一种具有抗炎等药理作用的活性成分；然而，其在类风湿关节炎（RA）中的作用机制尚未阐明。先前的研究表明，栀子苷通过调节整合素β 1（Itgβ1）介导的 Ras-Erk1/2 信号通路在 RA 中发挥治疗作用。然而，GE 对 Itgβ1 的作用机制尚不清楚。最近的证据表明，microRNAs（miRNAs）参与了 RA 的发生发展。在本研究中，我们开发了一种基于 miRNA-124a 的滑膜细胞修复策略。我们证明 miRNA-124a 可以直接抑制 Itgβ1 基因的表达，并在体外减少 TNF-α 刺激的细胞增殖。MH7A 细胞取自 RA 患者，并在 TNF-α（10ng/ml）存在的情况下用 GE 处理。此外，我们证明 miRNA-124a 的表达可以被 GE 调节。GE 上调 miRNA-124a 的表达，降低 Itgβ1 的表达在 mRNA 和蛋白水平上。本研究结果首次表明，GE 通过上调 miRNA-124a 的表达抑制 TNF-α 刺激的细胞增殖，并阻断 Ras-Erk1/2 通路的激活。我们的研究阐明了 miRNA-124a 在 RA 中作为一种保护性 miRNA 的作用，可能为未来 RA 的诊断和治疗提供新的策略。
