MicroRNA-24 通过靶向 Wnt 家族成员 4/Dvl-1/β-Catenin 信号通路对心肌梗死后大鼠心肌纤维化的影响

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Zhenhui Qi, Ling Tong, Jinxi Huang, Qingfeng Su
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引用次数: 0

摘要

在这项研究中,我们研究了 miR-24 对心肌梗死(MI)后大鼠心肌纤维化严重程度的影响,并探讨了其潜在机制。我们建立了 MI 诱导的心肌纤维化大鼠模型,并通过超声心动图评估心功能。我们采用 Western 印迹法和 RT-qPCR 法研究了 agomiR-24 对主要纤维化标志物(包括 COL1A1、COL3A1 和 α-SMA)的影响。微阵列分析、通路富集和蛋白相互作用网络分析揭示了受 agomiR-24 影响的信号通路和基因。我们分离了原代大鼠心脏成纤维细胞(CFs),并利用荧光素酶报告实验证实了 miR-24 的直接靶标。我们调节了 miR-24 在 CFs 中的表达,并通过 CCK-8 和 Transwell 试验分别评估了细胞的增殖和侵袭。此外,我们还通过 Western 印迹法研究了 miR-24 对 Wnt4/Dvl-1/β-catenin 信号通路的影响。最后,我们通过 RT-qPCR 检测了关键基因(Cyclin D1、p27、p21、MMP-3 和 MMP-9)的 mRNA 表达水平。我们的研究结果表明,agomiR-24 可改善大鼠心肌组织的心脏功能并减少纤维化标志物的表达。MiR-24 可通过靶向 Wnt4/Dvl-1/β- catenin 信号抑制 CF 的增殖和侵袭。它还能调节细胞增殖和基质重塑相关基因的 mRNA 表达。总之,我们的研究表明,miR-24 可通过抑制 Wnt4/Dvl- 1/β-catenin 通路来减轻心肌梗死后大鼠的心肌纤维化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effects of MicroRNA-24 on Myocardial Fibrosis in Rats After Myocardial Infarction by Targeting Wnt Family Member 4/Dvl-1/β-Catenin Signaling Pathway
In this study, we investigated the impact of miR-24 on myocardial fibrosis severity in rats following myocardial infarction (MI) and explored its underlying mechanisms. We established an MI-induced myocardial fibrosis rat model and assessed cardiac function via echocardiography. We employed Western blotting and RT-qPCR to examine the effects of agomiR-24 on key fibrotic markers, including COL1A1, COL3A1, and α-SMA. Microarray analysis, pathway enrichment, and proteinprotein interaction network analysis revealed the signaling pathways and genes influenced by agomiR-24. Primary rat cardiac fibroblasts (CFs) were isolated, and miR-24’s direct target was confirmed using luciferase reporter assays. We modulated miR-24 expression in CFs and assessed cell proliferation and invasion through CCK-8 and Transwell assays, respectively. Furthermore, we investigated the impact of miR-24 on the Wnt4/Dvl-1/β-catenin signaling pathway by Western blotting. Finally, we examined mRNA expression levels of key genes (Cyclin D1, p27, p21, MMP-3, and MMP-9) through RT-qPCR. Our findings demonstrated that agomiR-24 improved cardiac function and reduced fibrotic marker expression in rat myocardial tissues. MiR-24 inhibited CF proliferation and invasion, potentially by targeting Wnt4/Dvl-1/β- catenin signaling. It also regulated mRNA expression of genes associated with cell proliferation and matrix remodeling. Overall, our study suggests that miR-24 may attenuate myocardial fibrosis in post-MI rats by suppressing the Wnt4/Dvl- 1/β-catenin pathway.
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
期刊介绍: ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.
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