Feng Xueqiang, Yao Fuwang, Lang Yuqin, Cao Zhibin
Department of Vascular Intervention, Affiliated Hospital of Weifang Medical University Weifang, Shandong Province, China.
Department of Anesthesiology, Affiliated Hospital of Weifang Medical University Weifang, Shandong Province, China.
Am J Transl Res. 2022 Jun 15;14(6):4251-4259. eCollection 2022.
Atherosclerosis (AS) is a chronic inflammatory disease with high mortality. miRNAs perform a vital role in its development. This study aimed to discuss the effect of miR-145 in AS occurrence and development.
The effects of miR-145 mimics and inhibitors on IL-6, IL-1β and TNF-α expressions were assessed by qRT-PCR and ELISA. CCK-8 was applied to examine the influence of miR-145 on macrophage proliferation. The influence of miR-145 on the QKI transcriptional activity was analyzed using luciferase reporter gene assy.
Overexpression of miR-145 could enhance the expression of IL-6, IL-1β, and TNF-α. Down-regulation of miR-145 could inhibit the proliferation of macrophages and the expression level of inflammatory cytokines. The effect of miR-145 inhibitor on the expression of inflammatory factors was partially reversed by interfering with the transcription of QKI with siRNA.
miR-145 regulates the inflammatory response induced by macrophage activation through targeting QKI. It provides a means for AS targeted therapy.
动脉粥样硬化(AS)是一种死亡率很高的慢性炎症性疾病。微小RNA(miRNA)在其发展过程中发挥着至关重要的作用。本研究旨在探讨miR-145在AS发生发展中的作用。
通过定量逆转录聚合酶链反应(qRT-PCR)和酶联免疫吸附测定(ELISA)评估miR-145模拟物和抑制剂对白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)表达的影响。采用细胞计数试剂盒-8(CCK-8)检测miR-145对巨噬细胞增殖的影响。利用荧光素酶报告基因检测分析miR-145对QKI转录活性的影响。
miR-145过表达可增强IL-6、IL-1β和TNF-α的表达。miR-145表达下调可抑制巨噬细胞增殖和炎性细胞因子的表达水平。用小干扰RNA(siRNA)干扰QKI的转录可部分逆转miR-145抑制剂对炎性因子表达的影响。
miR-145通过靶向QKI调节巨噬细胞激活诱导的炎症反应。这为AS的靶向治疗提供了一种手段。