MicroRNA-326 contributes to autoimmune thyroiditis by targeting the Ets-1 protein
MicroRNA-326 contributes to autoimmune thyroiditis by targeting the Ets-1 protein
复制标题
MicroRNA-326 通过靶向 Ets-1 蛋白导致自身免疫性甲状腺炎
DOI：
10.1007/s12020-017-1465-4
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Li Yushu
中科院分区：
文献类型：
--
作者：
Zhao Na;Zou Hongjin;Qin Jing;Fan Chenling;Liu Yongping;Wang Shuo;Shan Zhongyan;Teng Weiping;Li Yushu
microRNA -326 （miR-326）作为microRNA （miRNA）家族的一员，包括内源性单链、保守的非编码小rna，已被报道在多发性硬化症和系统性红斑狼疮等自身免疫性疾病中发挥重要作用。然而，关于miR-326在自身免疫性甲状腺炎（AIT）中的作用的研究很少发表。本文探讨了miR-326及其通路在碘诱导AIT中的作用。方法将人类AIT模型小鼠snod . h- 2h4随机分为正常水对照组和高碘组。高碘组小鼠给予0.05% NaI（~1000倍于正常日碘摄入量），对照组小鼠给予无菌水。此外，我们在体外脾脏单核细胞实验中评估了小干扰RNA （siRNA）的干扰。结果本研究发现，在碘诱导的甲状腺炎小鼠模型中，Th17细胞显著增加，miR-326高表达。此外，Th17分化负调控因子Ets-1蛋白的表达显著降低。有趣的是，我们的分析显示，在AIT小鼠中，Ets-1蛋白表达与miR-326水平呈负相关（r= - 0.814,p< 0.01）。我们的研究表明，在AIT的发生和发展过程中，miR-326抑制Ets-1蛋白的表达，促进Th17细胞的分化。miR-326抑制剂的加入逆转了Th17细胞的产生和Ets-1蛋白的表达，支持了这一假设。结论本研究结果提示miR-326可能靶向Ets-1蛋白参与碘化物诱导的甲状腺炎，为利用miRNA靶向治疗自身免疫性疾病提供了新的理论依据。
PurposeMicroRNA-326 (miR-326), as a member of the microRNA (miRNA) family, which includes endogenous single-stranded, conserved, noncoding small RNAs, has been reported to play important roles in autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus. However, few studies of the role of miR-326 in autoimmune thyroiditis (AIT) have been published. Here, we explored the roles of miR-326 and the involved pathway in iodine-induced AIT.MethodsNOD.H-2h4mice, which are a model of human AIT, were randomly divided into a normal water control group and a high-iodine group. Mice in the high-iodine group were administered 0.05% NaI (~1000 times the normal daily iodine intake), and mice in the control group received sterile water. Furthermore, we evaluated small interfering RNA (siRNA) interference in spleen mononuclear cell experiments in vitro.ResultsIn this study, we found that Th17 cells were significantly increased with a high expression of miR-326 in an iodine-induced thyroiditis NOD.H-2h4mouse model. In addition, the expression of Ets-1 protein, a negative regulator of Th17 differentiation, was significantly decreased. Intriguingly, our analysis showed that Ets-1 protein expression was negatively correlated with miR-326 levels in AIT mice (r= −0.814,p< 0.01). Our study indicated that miR-326 inhibited Ets-1 protein expression and promoted the differentiation of Th17 cells during the onset and development of AIT. The addition of a miR-326 inhibitor reversed Th17 cell production and Ets-1 protein expression, supporting this hypothesis.ConclusionsThe results of our study suggest that miR-326 may target the Ets-1 protein to contribute to iodide-induced thyroiditis, providing a new theoretical basis for the use of miRNA targeting therapy for the treatment of autoimmune diseases.
登录
查看更多内容
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
30.5
作者：
Du, Changsheng;Liu, Chang;Pei, Gang
通讯作者：
Pei, Gang
影响因子：
3.2
作者：
Hiroya Yamada;M. Itoh;I. Hiratsuka;S. Hashimoto
通讯作者：
Hiroya Yamada;M. Itoh;I. Hiratsuka;S. Hashimoto
DOI：
10.1084/jem.178.3.793
发表时间：
1993-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Podolin PL;Pressey A;DeLarato NH;Fischer PA;Peterson LB;Wicker LS
通讯作者：
Wicker LS
影响因子：
64.8
作者：
Thermann, Rolf;Hentze, Matthias W.
通讯作者：
Hentze, Matthias W.