miR-21 通过靶向 Wnt 信号通路缓解大鼠类风湿关节炎。
MiR-21 relieves rheumatoid arthritis in rats via targeting Wnt signaling pathway.
机构信息
Department of Rheumatology, 970 Hospital of the Chinese People's Liberation Army, Weihai, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Aug;23(3 Suppl):96-103. doi: 10.26355/eurrev_201908_18635.
OBJECTIVE
To investigate the influence of micro ribonucleic acid (miR)-21 on rats with rheumatoid arthritis (RA) through the Wnt signaling pathway.
MATERIALS AND METHODS
A total of 30 rats were divided into three groups: control group (healthy rats, n=10), model group (rat model of RA, n=10), and MiR group (rat model of RA injected with miR-21 lentivirus, n=10). The paw volume, arthritis indexes, and protein expression level in each group were analyzed by means of paw volume and arthritis index measurement, reverse transcription-polymerase chain reaction (RT-PCR) assay, and fluorescent Western blotting.
RESULTS
The expression levels of inflammatory factors declined in MiR group compared with those in model group, while they were higher in model group than those in control group and MiR group (p<0.05). At 15 d after transfection with lentivirus, the paw volume in MiR group was smaller than that in model group, which was decreased markedly with the extended time of transfection (p<0.05). On the 30th d, MiR group had a remarkably smaller paw volume than model group. In comparison with that in control group, the paw volume in model group was increased notably from the 7th d and displayed a significant difference in the 30th d (p<0.05). The arthritis indexes in MiR group were lower than those in model group; however, there were no apparent inflammations at the joints at 15 d after drug administration. Moreover, the longer the time of drug administration was, the less apparent the inflammations at the joints will be. The inflammations at the joints were ameliorated evidently on the 30th d in MiR group (p<0.05). Compared with those in control group, the inflammations in model group were increased significantly from the 7th d, with significant differences in the 30th d (p<0.05). The messenger RNA (mRNA) expression levels of interleukin-6 (IL-6), IL-8, and Wnt in MiR group were higher than those in control group, but lower than those in model group (p<0.05), while they were higher in model group than those in control group (p<0.05). The expression level of Wnt protein was decreased in MiR group compared with that in model group (p<0.05), and model group had a prominently elevated expression level of Wnt protein in comparison with control group (p<0.05).
CONCLUSIONS
MiR-21 overexpression can repress the expressions of IL-6 and IL-8 and relieve the symptoms of RA by down-regulating the Wnt signal.
目的
通过 Wnt 信号通路研究微小 RNA（miR）-21 对类风湿关节炎（RA）大鼠的影响。
材料与方法
将 30 只大鼠分为对照组（健康大鼠，n=10）、模型组（RA 大鼠模型，n=10）和 miR 组（RA 大鼠模型注射 miR-21 慢病毒，n=10）。通过测量足体积和关节炎指数、逆转录-聚合酶链反应（RT-PCR）检测和荧光 Western 印迹分析，分析各组大鼠的足体积、关节炎指数和蛋白表达水平。
结果
与模型组相比，miR 组的炎症因子表达水平降低，而与对照组和 miR 组相比，模型组的炎症因子表达水平升高（p<0.05）。慢病毒转染后 15d，miR 组大鼠的足体积小于模型组，且随着转染时间的延长，大鼠的足体积明显减小（p<0.05）。第 30 天，miR 组大鼠的足体积明显小于模型组。与对照组相比，模型组大鼠的足体积从第 7 天开始明显增加，第 30 天差异有统计学意义（p<0.05）。miR 组大鼠的关节炎指数低于模型组；然而，药物治疗后 15d 时关节未见明显炎症。此外，随着药物治疗时间的延长，关节炎症越不明显。在第 30 天，miR 组大鼠的关节炎症明显改善（p<0.05）。与对照组相比，模型组大鼠从第 7 天开始炎症明显增加，第 30 天差异有统计学意义（p<0.05）。miR 组大鼠白细胞介素 6（IL-6）、白细胞介素 8（IL-8）和 Wnt 的信使 RNA（mRNA）表达水平高于对照组，但低于模型组（p<0.05），而模型组高于对照组（p<0.05）。与模型组相比，miR 组大鼠的 Wnt 蛋白表达水平降低（p<0.05），模型组大鼠的 Wnt 蛋白表达水平明显高于对照组（p<0.05）。
结论
miR-21 过表达通过下调 Wnt 信号抑制 IL-6 和 IL-8 的表达，缓解 RA 症状。
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