miR-448-3p通过调节KLF5的表达抑制颅内动脉瘤进展

目的:明确mi R-448-3p对颅内动脉瘤发展的影响。方法:我们通过结扎左侧肾动脉和左侧颈总动脉的方法建立大鼠IA模型;qRT-PCR用于检测mi R-448-3p表达;qRT-PCR和western blot用于检测KLF5 m RNA和蛋白表达;qRT-PCR和ELISA法用于检测炎症因子水平。结果:我们发现IA诱导大鼠中mi R-448-3p表达下调,而KLF5表达上调。我们发现并鉴定出KLF5是平滑肌细胞中mi R-448-3p的直接靶点。此外,mi R-448-3p处理使得IA诱导4周后动脉瘤大小和瘤腔截面积变小。mi R-448-3p处理保护了IA诱导后的壁厚比,抑制了巨噬细胞浸润。IAs引起KLF5表达显著增加,被mi R-448-3p处理后表达显著降低。我们还发现mi R-448-3p在脂多糖诱导的RAW 264.7巨噬细胞中具有抗炎作用。脂多糖促进KLF5、MMP2、MMP9的表达水平,但却被mi R-448-3p所抑制。结论:研究结果表明,mi R-448-3p可以抑制IA的进展,其机制可能是通过下调KLF5的介导的炎症反应。

miR-448-3p Suppressed Intracranial Aneurysm by Inhibiting KLF5 Expression

ABSTRACT Objective: To determine the function of miR-448-3p inintracranial aneurysm (IA) development. Methods: We created a rat model of IA by ligating the left renal artery and the left common carotid artery. The expression of miR-448-3p was detected by qRT-PCR assay, and KLF5 mRNA and protein levels were measured by qRT-PCR and western blot. Inflammatory cytokines were measured by qRT-PCR and ELISA assay. Results: We found that miR-448-3p was decreased and KLF5 was increased in IA rats. We showed that KLF5 was a direct target of miR-448-3p in SMCs. In addition, aneurysms size and the lumen area of the aneurysms were smaller 4 weeks after IA induction in the miR-448-3p-treated IA rats. miR-448-3p treatment protected the wall thickness ratio and inhibited macrophage infiltration after IA induction. IA caused an increase in KLF5 expression and miR-448-3p alleviated KLF5 expression Moreover, the anti-inflammatory effect of miR-448-3p was verified in lipopolysaccharide -stimulated RAW 264.7 macrophage cells. The expression levels of KLF5, MMP2, and MMP9 levels were elevated by LPS, and were attenuated by miR-448-3p. Conclusion: All data indicate that miR-448-3p have the inhibitory role in IA progression, suggesting that miR-448-3p is crucial for preventing the development of IA through suppressing the macrophage-mediated inflammation.