Chen Xiaoying, Li Wenting, Li Liping, Ying Lei, Liu Xiaohui, Ke Jiangwei
Department of Clinical Laboratory, Children's Hospital of Jiangxi, Nanchang, CHN.
Department of Rheumatology and Immunology, Children's Hospital of Jiangxi, Nanchang, CHN.
Cureus. 2025 Jun 11;17(6):e85809. doi: 10.7759/cureus.85809. eCollection 2025 Jun.
The pathogenesis of juvenile idiopathic arthritis (JIA) has not yet been clarified and is closely related to persistent overactivation of the JAK/STAT signaling pathway. MicroRNA (miRNA)-223 (miR-223) and miRNA-132 (miR-132) might be involved in the development of JIA. However, the mechanism underlying the pathogenesis of JIA is unclear. In this study, we investigated the roles and molecular mechanisms of serum exosomal miR-223 and miR-132 in JIA. Methods: Patients with systemic JIA were selected as the systemic group (sJIA), patients with polyarticular JIA and oligoarticular JIA were selected as the articular group (aJIA), and healthy children who underwent physical examinations at the same time were selected as the normal control group (NC). Exosomes were extracted from the serum, and the purified exosomes were subjected to electron microscopy to observe their particle morphology. The particle size distribution and concentration of the exosomes were detected by an N30E particle size analyzer. The expression levels of miR-223 and miR-132 in exosomes were quantitatively detected by the SYBR green method. The protein levels of STAT3 and SOCS3 were detected by Western blot.
The expression level of miR-223 in serum exosomes of the sJIA group was significantly higher than in the aJIA group and the NC group (4.04±0.34 vs. 1.52±0.30, 0.88±0.17), and the difference was statistically significant (P<0.001). However, the expression level of miR-132 in serum exosomes of the sJIA group was significantly lower than in the aJIA group and the NC group (0.09±0.01 vs. 0.17±0.02, 0.94±0.08), and the difference was statistically significant (P<0.001). The expression levels of serum interleukin (IL)-6, IL-8, and IL-10 in the sJIA group were significantly higher than those in the aJIA group and the NC group; the difference was statistically significant (P<0.001). The IL-17 expression in the sJIA group and aJIA group was significantly greater than the expression levels in the NC groups (P<0.001). The expression level of miR-223 in exosomes was positively correlated with the expression levels of the clinical inflammatory factors IL-6, IL-8, IL-10, and IL-17 (P<0.001). However, the expression level of miR-132 in exosomes was negatively correlated with the expression levels of clinical inflammatory factors of IL-6, IL-8, IL-10, and IL-17 (P<0.001). The expression level of SOCS3 protein in both the sJIA and aJIA groups was significantly higher than in the NC group (0.25±0.05 and 0.21±0.03 vs. 0.10±0.02, respectively), and the difference was statistically significant (P<0.05). Regrettably, there was no significant difference yet in the expression level of STAT3 in the three groups (P>0.05).
miR-223 and miR-132 may be two potential new markers of JIA, providing new ideas for diagnostic tests and therapeutic interventions. But larger studies are needed to confirm these findings and assess their generalizability across diverse populations. miR-223 may promote inflammation in JIA patients by enhancing the JAK/STAT signaling pathway, while miR-132 may reduce inflammation in JIA patients by inhibiting the JAK/STAT signaling pathway. Its inhibitory effect may be closely related to SOCS3 through the JAK/STAT signaling pathway.
幼年特发性关节炎（JIA）的发病机制尚未阐明，且与JAK/STAT信号通路的持续过度激活密切相关。微小RNA（miRNA）-223（miR-223）和miRNA-132（miR-132）可能参与JIA的发病过程。然而，JIA发病机制背后的机制尚不清楚。在本研究中，我们调查了血清外泌体miR-223和miR-132在JIA中的作用和分子机制。方法：选择全身型JIA患者作为全身型组（sJIA），多关节型JIA和少关节型JIA患者作为关节型组（aJIA），同时选择进行体检的健康儿童作为正常对照组（NC）。从血清中提取外泌体，对纯化的外泌体进行电子显微镜观察其颗粒形态。通过N30E粒度分析仪检测外泌体的粒度分布和浓度。采用SYBR green法定量检测外泌体中miR-223和miR-132 的表达水平。通过蛋白质印迹法检测STAT3和SOCS3的蛋白水平。
sJIA组血清外泌体中miR-223的表达水平显著高于aJIA组和NC组（4.04±0.34对1.52±0.30，0.88±0.17），差异具有统计学意义（P<0.001）。然而，sJIA组血清外泌体中miR-132的表达水平显著低于aJIA组和NC组（0.09±0.01对0.17±0.02，0.94±0.08），差异具有统计学意义（P<0.001）。sJIA组血清白细胞介素（IL）-6、IL-8和IL-10的表达水平显著高于aJIA组和NC组；差异具有统计学意义（P<0.001）。sJIA组和aJIA组的IL-17表达显著高于NC组（P<0.001）。外泌体中miR-223的表达水平与临床炎症因子IL-6、IL-8、IL-10和IL-17的表达水平呈正相关（P<0.001）。然而，外泌体中miR-132的表达水平与IL-6、IL-8、IL-10和IL-17的临床炎症因子表达水平呈负相关（P<0.001）。sJIA组和aJIA组中SOCS3蛋白的表达水平均显著高于NC组（分别为0.25±0.05和0.21±0.03对0.10±0.02），差异具有统计学意义（P<0.05）。遗憾的是，三组中STAT3的表达水平尚无显著差异（P>0.05）。
miR-223和miR-132可能是JIA的两个潜在新标志物，为诊断测试和治疗干预提供了新的思路。但需要更大规模的研究来证实这些发现并评估其在不同人群中的普遍性。miR-223可能通过增强JAK/STAT信号通路促进JIA患者的炎症反应，而miR-132可能通过抑制JAK/STAT信号通路减轻JIA患者的炎症反应。其抑制作用可能通过JAK/STAT信号通路与SOCS3密切相关。
