The anti-inflammatory effect of microRNA-383-3p interacting with IL1R2 against homocysteine-induced endothelial injury in rat coronary arteries (Retracted article. See vol. 122, 2021)
The anti-inflammatory effect of microRNA-383-3p interacting with IL1R2 against homocysteine-induced endothelial injury in rat coronary arteries (Retracted article. See vol. 122, 2021)
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DOI：
10.1002/jcb.26854
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发表时间：
2018-08-01
影响因子：
4
通讯作者：
Wang, Jia-Wang
中科院分区：
文献类型：
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作者：
Lian, Zheng;Lv, Feng-Feng;Wang, Jia-Wang
MicroRNAs （miRs）被广泛报道为参与冠状动脉粥样硬化（CAS）过程的新型生物标志物。因此，本研究旨在探讨靶向IL1R2的miR-383-3p在CAS冠状动脉内皮细胞（CAECs）炎症损伤中的作用。在同型半胱氨酸（HCY）诱导的caec中，miR-383-3p的潜在调控机制与miR-383-3p模拟物、miR-383-3p抑制剂以及miR-383-3p抑制剂和siRNA联合抗IL1R2的治疗相一致。采用MTT法、Hoechst 33258染色法和成管法分别测定细胞活力、细胞凋亡和成管率。ELISA法检测各组IL-1、IL-6、IL-10、IL-18水平。双荧光素酶报告基因检测证实IL1R2是miR-383-3p的靶基因。AS大鼠心肌组织中MiR-383-3p下调，IL1R2互反。上调miR-383-3p可降低hcy诱导caec中il - 1r2、caspase-1、IL-1、IL-6、IL-18的表达水平及细胞凋亡率，提高IL-10的表达、细胞活力和成管能力。这些结果在miR-383-3p抑制剂治疗的hcy诱导的caec中是禁忌的。综上所述，miR-383-3p介导的IL1R2通过抑制炎性体信号通路的激活来阻止hcy诱导的caec细胞凋亡和炎症损伤。这些发现高度提示miR-383-3p可能在预防CAS和其他心血管疾病中有益。
MicroRNAs (miRs) are widely reported to be novel biomarkers involved in the process of coronary atherosclerosis (CAS). Hence, this study aims to explore the function of miR-383-3p targeting IL1R2 on inflammatory injury of coronary artery endothelial cells (CAECs) in CAS. The underlying regulatory mechanisms of miR-383-3p were analyzed in concert with the treatment of miR-383-3p mimics, miR-383-3p inhibitors, and the combination of miR-383-3p inhibitors and siRNA against IL1R2 in homocysteine (HCY)-induced CAECs. MTT, Hoechst 33258 staining, and tube formation assay were employed in order to measure cell viability, apoptosis, and tube formation, respectively. The levels of IL-1, IL-6, IL-10, and IL-18 were determined by ELISA. IL1R2 was verified as the target gene of miR-383-3p by dual-luciferase reporter gene assay. MiR-383-3p was down-regulated in myocardial tissues of AS rats while IL1R2 was the reciprocal. The up-regulation of miR-383-3p decreased the levels of IL1R2, caspase-1, IL-1, IL-6, and IL-18 expressions, as well as cell apoptosis rate in the HCY-induced CAECs, while IL-10 expression, cell viability, and tube formation ability were increased. These results were contraindicated in the HCY-induced CAECs treated by miR-383-3p inhibitors. In conclusion, miR-383-3p mediating IL1R2 prevents HCY-induced apoptosis and inflammation injury in CAECs through the inhibition of the activation of inflammasome signaling pathway. These findings highly indicate that miR-383-3p may be beneficial in the prevention of CAS and other cardiovascular diseases.