NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages.

IF 1.7 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Open Medicine Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI:10.1515/med-2024-1072
Tingyu Jin, Han Gao, Danyang Meng, Man Luo, Jin Hu
{"title":"NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages.","authors":"Tingyu Jin, Han Gao, Danyang Meng, Man Luo, Jin Hu","doi":"10.1515/med-2024-1072","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke associated with atherosclerosis is globally named atherothrombotic stroke. Presently, the underlying pathogenic genes promoting carotid atherosclerotic plaques transfer from a stable to unstable state remains elusive. This study aims to find the hub genes disturbing the stability of plaques and explore the primary cells affected by these hub genes.</p><p><strong>Methods: </strong>The optimal hub genes from five datasets for unstable plaques were identified by overlapping genes derived from Boruta and LASSO algorithms. The hub genes' expression levels in stroke patients were confirmed through RT-qPCR. Visualization of the hub genes' expression across various cell clusters was achieved with the aid of the Seurat R package. Then, hub genes were overexpressed or knock-down by lentivirus and siRNA, respectively. The inflammatory factors in the culture medium were detected using an ELISA assay.</p><p><strong>Results: </strong>Eight genes (APOD, ASXL1, COL4A5, HTR7, INF2, NSUN6, PDSS2, and RBBP7) were identified and confirmed by RT-qPCR. The prognostic model was built upon this eight-gene composite foundation, and the area under the curve was 0.98. Based on CIBERSORT findings, unstable plaques displayed a higher macrophage proportion compared to stable ones (<i>P</i> < 0.05). These eight genes also correlated with infiltrated immune cells, especially macrophages. Then, according to single-cell RNA-seq analysis, we found that the eight hub genes mainly expressed in macrophages. The cellular localization of two hub genes (NSUN6 and HTR7) with high distinguishability was confirmed, and gene set enrichment analysis also clarified the possible biological pathways regulated by them. The findings from the <i>in vitro</i> investigation revealed that TNF-α and IL-6 were reduced in macrophages with NSUN6 overexpression or HTR7 knockdown.</p><p><strong>Conclusion: </strong>Eight hub genes, especially NSUN6 and HTR7, were found to promote the progression of plaques by regulating the immune responses of macrophages.</p>","PeriodicalId":19715,"journal":{"name":"Open Medicine","volume":"19 1","pages":"20241072"},"PeriodicalIF":1.7000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500533/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Open Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1515/med-2024-1072","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Ischemic stroke associated with atherosclerosis is globally named atherothrombotic stroke. Presently, the underlying pathogenic genes promoting carotid atherosclerotic plaques transfer from a stable to unstable state remains elusive. This study aims to find the hub genes disturbing the stability of plaques and explore the primary cells affected by these hub genes.

Methods: The optimal hub genes from five datasets for unstable plaques were identified by overlapping genes derived from Boruta and LASSO algorithms. The hub genes' expression levels in stroke patients were confirmed through RT-qPCR. Visualization of the hub genes' expression across various cell clusters was achieved with the aid of the Seurat R package. Then, hub genes were overexpressed or knock-down by lentivirus and siRNA, respectively. The inflammatory factors in the culture medium were detected using an ELISA assay.

Results: Eight genes (APOD, ASXL1, COL4A5, HTR7, INF2, NSUN6, PDSS2, and RBBP7) were identified and confirmed by RT-qPCR. The prognostic model was built upon this eight-gene composite foundation, and the area under the curve was 0.98. Based on CIBERSORT findings, unstable plaques displayed a higher macrophage proportion compared to stable ones (P < 0.05). These eight genes also correlated with infiltrated immune cells, especially macrophages. Then, according to single-cell RNA-seq analysis, we found that the eight hub genes mainly expressed in macrophages. The cellular localization of two hub genes (NSUN6 and HTR7) with high distinguishability was confirmed, and gene set enrichment analysis also clarified the possible biological pathways regulated by them. The findings from the in vitro investigation revealed that TNF-α and IL-6 were reduced in macrophages with NSUN6 overexpression or HTR7 knockdown.

Conclusion: Eight hub genes, especially NSUN6 and HTR7, were found to promote the progression of plaques by regulating the immune responses of macrophages.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
NSUN6 和 HTR7 通过调节巨噬细胞的免疫反应扰乱了颈动脉粥样硬化斑块的稳定性。
背景:与动脉粥样硬化相关的缺血性中风在全球被命名为动脉粥样硬化血栓性中风。目前,促进颈动脉粥样硬化斑块从稳定状态向不稳定状态转移的潜在致病基因仍未确定。本研究旨在找到干扰斑块稳定性的枢纽基因,并探索受这些枢纽基因影响的原代细胞:方法:通过Boruta和LASSO算法得出的重叠基因,从五个数据集中识别出不稳定斑块的最佳枢纽基因。通过 RT-qPCR 确认了中风患者中枢基因的表达水平。借助 Seurat R 软件包实现了枢纽基因在不同细胞簇中表达的可视化。然后,通过慢病毒和 siRNA 分别过表达或敲除中枢基因。培养基中的炎症因子用酶联免疫吸附试验检测:结果:8个基因(APOD、ASXL1、COL4A5、HTR7、INF2、NSUN6、PDSS2和RBBP7)被识别出来,并通过RT-qPCR得到确认。预后模型就是在这八个基因的复合基础上建立起来的,其曲线下面积为 0.98。根据 CIBERSORT 的发现,与稳定斑块相比,不稳定斑块的巨噬细胞比例更高(P < 0.05)。这八个基因还与浸润的免疫细胞,尤其是巨噬细胞相关。然后,根据单细胞RNA-seq分析,我们发现这8个中心基因主要在巨噬细胞中表达。两个区分度较高的枢纽基因(NSUN6 和 HTR7)的细胞定位得到了证实,基因组富集分析也明确了它们可能调控的生物学通路。体外研究结果显示,NSUN6过表达或HTR7敲除的巨噬细胞中TNF-α和IL-6减少:结论:研究发现八个枢纽基因,尤其是 NSUN6 和 HTR7,通过调节巨噬细胞的免疫反应促进斑块的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Open Medicine
Open Medicine Medicine-General Medicine
CiteScore
3.00
自引率
0.00%
发文量
153
审稿时长
20 weeks
期刊介绍: Open Medicine is an open access journal that provides users with free, instant, and continued access to all content worldwide. The primary goal of the journal has always been a focus on maintaining the high quality of its published content. Its mission is to facilitate the exchange of ideas between medical science researchers from different countries. Papers connected to all fields of medicine and public health are welcomed. Open Medicine accepts submissions of research articles, reviews, case reports, letters to editor and book reviews.
期刊最新文献
Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study. Iron in ventricular remodeling and aneurysms post-myocardial infarction.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1