miR-378-3p通过负向调节ATG12减轻挫伤脊髓损伤

IF 1.8 4区 医学 Q3 PATHOLOGY International Journal of Experimental Pathology Pub Date : 2021-10-28 DOI:10.1111/iep.12400
Haocong Zhang, Hailong Yu, Huifeng Yang, Yang Zhan, Xinwei Liu
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引用次数: 4

摘要

MicroRNAs (miRNAs或miRs)在脊髓损伤(SCI)的发病过程中起重要作用。本研究探讨了miR-378-3p和自噬相关12 (autophagy-related 12, ATG12)在SCI中的作用。RT-qPCR检测miR-378-3p、ATG12 mRNA表达水平。采用CCK-8和LDH检测细胞活力和膜完整性。为了分析miR-378-3p与ATG12之间的相互作用,我们进行了双荧光素酶报告基因检测。采用Basso, Beattie和Bresnahan评分法检测大鼠后肢功能,并采用运动缺陷指数评分法评价神经功能。通过这些方法,我们发现miR-378-3p在脊髓损伤组织和缺氧细胞中表达下调,而ATG12表达上调。缺氧通过缺氧诱导因子1-α抑制miR-378-3p的表达。过表达miR-378-3p通过直接抑制ATG12对神经细胞产生抗凋亡作用。miR-378-3p的输注改善了挫伤性脊髓损伤大鼠后肢运动功能和神经功能,有助于改善功能缺陷,缓解挫伤性脊髓损伤。因此,我们得出结论,在PC12或N2A细胞中上调miR-378-3p的表达可抑制神经细胞的凋亡,在挫伤性脊髓损伤模型大鼠中给予miR-378-3p可改善神经和运动功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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miR-378-3p alleviates contusion spinal cord injury by negatively regulating ATG12

MicroRNAs (miRNAs or miRs) serve essential roles in the pathogenic process of spinal cord injury (SCI). The present study investigated the role of miR-378-3p and autophagy-related 12 (ATG12) in SCI. RT-qPCR was used to detect the mRNA expression levels of miR-378-3p and ATG12. Cell viability and membrane integrity were evaluated using CCK-8 and LDH assays. For the analysis of the interaction between miR-378-3p and ATG12, a dual-luciferase reporter assay was conducted. The hindlimb function of rats was detected with the Basso, Beattie and Bresnahan score, and the motor deficit index score was used to evaluate nerve function. Using these approaches, it was identified that miR-378-3p expression was downregulated, while that of ATG12 was upregulated in SCI tissues and in cells exposed to hypoxia. Hypoxia repressed the expression of miR-378-3p via hypoxia-inducible factor 1-α. The overexpression of miR-378-3p exerted anti-apoptotic effects on nerve cells by directly repressing ATG12. The infusion of miR-378-3p improved hindlimb motor function and the neurological functions of rats with contusion SCI, which contributed to amelioration of functional deficits and the relief of contusion SCI. Therefore, it was concluded that upregulated expression of miR-378-3p in PC12 or N2A cells repressed the apoptosis of nerve cells, and the administration of miR-378-3p in model rats with contusion SCI improved neurological and motor functions.

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来源期刊
CiteScore
4.50
自引率
3.30%
发文量
35
审稿时长
>12 weeks
期刊介绍: Experimental Pathology encompasses the use of multidisciplinary scientific techniques to investigate the pathogenesis and progression of pathologic processes. The International Journal of Experimental Pathology - IJEP - publishes papers which afford new and imaginative insights into the basic mechanisms underlying human disease, including in vitro work, animal models, and clinical research. Aiming to report on work that addresses the common theme of mechanism at a cellular and molecular level, IJEP publishes both original experimental investigations and review articles. Recent themes for review series have covered topics as diverse as "Viruses and Cancer", "Granulomatous Diseases", "Stem cells" and "Cardiovascular Pathology".
期刊最新文献
Issue Information Thrombospondins: Conserved mediators and modulators of metazoan extracellular matrix Renal protective roles of macrophage matrix metalloproteinase-12 in mice with obstructed kidneys Feline hypertrophic cardiomyopathy: Does the microRNA-mRNA regulatory network contribute to heart sarcomeric protein remodelling? Zinc transporter ZnT5 is associated with epithelial mesenchymal transition via SMAD1 in breast cancer
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