缺血性脑卒中中焦氧中枢基因和炎症细胞类型相关基因的鉴定。

IF 4.6 2区 医学 Q1 NEUROSCIENCES
Molecular Neurobiology Pub Date : 2025-05-01 Epub Date: 2025-01-03 DOI:10.1007/s12035-024-04647-x
Wei Ge, Liangbin Cao, Can Liu, Hao Wang, Meijing Lu, Yongquan Chen, Ye Wang
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引用次数: 0

摘要

中风是全球第二大死因。脑卒中后缺血-再灌注损伤(IRI)引发的免疫风暴损伤是巨大的。然而,关于IRI中焦亡的转录组动力学数据有限。本研究旨在分析脑卒中中关键焦亡基因的表达及其与免疫浸润的关系。从获得的大脑中动脉闭塞(MCAO)数据集中鉴定出与焦热相关的基因。进行了热缩相关基因的差异表达和功能分析,并确定了高危组和低危组之间功能富集的差异。选择差异表达的焦热相关基因构建MCAO诊断模型并进行验证。构建MCAO高危组和低危组,进行热死相关枢纽基因的表达和免疫细胞相关性分析。此外,还构建了与热降解相关的中枢基因与miRNA之间的调控网络,并对蛋白结构域进行了预测。用MCAO大鼠模型验证了关键焦亡基因的表达。25个焦亡基因出现差异表达,包括4个枢纽基因,即WISP2、MELK、SDF2L1和AURKB。特征基因采用实时定量PCR分析验证。高、低危组WISP2、MELK、SDF2L1的表达差异有统计学意义。在免疫浸润分析中,MCAO样品中有12个免疫细胞的表达存在差异。进一步分析表明,高危组中与热死相关的中枢基因SDF2L1与免疫细胞活化的树突状细胞和低危组中免疫细胞自然杀伤细胞之间存在显著正相关。本研究确定了4个与焦热相关的枢纽基因,其中WISP2、MELK和SDF2L1的表达升高与高危人群密切相关。免疫浸润中炎症细胞类型的分析可以预测缺血性卒中的风险水平,有助于促进治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identifying Pyroptosis-Hub Genes and Inflammation Cell Type-Related Genes in Ischemic Stroke.

Stroke is the second-leading global cause of death. The damage attributed to the immune storm triggered by ischemia-reperfusion injury (IRI) post-stroke is substantial. However, data on the transcriptomic dynamics of pyroptosis in IRI are limited. This study aimed to analyze the expression of key pyroptosis genes in stroke and their correlation with immune infiltration. Pyroptosis-related genes were identified from the obtained middle cerebral artery occlusion (MCAO) datasets. Differential expression and functional analyses of pyroptosis-related genes were performed, and differences in functional enrichment between high-risk and low-risk groups were determined. An MCAO diagnostic model was constructed and validated using selected pyroptosis-related genes with differential expression. High- and low-risk MCAO groups were constructed for expression and immune cell correlation analysis with pyroptosis-related hub genes. A regulatory network between pyroptosis-related hub genes and miRNA was also constructed, and protein domains were predicted. The expression of key pyroptosis genes was validated using an MCAO rat model. Twenty-five pyroptosis genes showed differential expression, including four hub genes, namely WISP2, MELK, SDF2L1, and AURKB. Characteristic genes were verified using real-time quantitative PCR analyses. The high- and low-risk groups showed significant expression differences for WISP2, MELK, and SDF2L1. In immune infiltration analysis, 12 immune cells showed differences in expression in MCAO samples. Further analysis demonstrated significant positive correlations between the pyroptosis-related hub gene SDF2L1 and immune cell-activated dendritic cells in the high-risk group and immune cell natural killer cells in the low-risk group. This study identified four pyroptosis-related hub genes, with elevated WISP2, MELK, and SDF2L1 expression closely associated with the high-risk group. The analysis of inflammatory cell types in immune infiltration can predict ischemic stroke risk levels and help to facilitate treatment.

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来源期刊
Molecular Neurobiology
Molecular Neurobiology 医学-神经科学
CiteScore
9.00
自引率
2.00%
发文量
480
审稿时长
1 months
期刊介绍: Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.
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