鉴定主动脉夹层中的关键铁死亡基因
To Identify the Key Ferroptosis Genes in Aortic Dissection
DOI: 10.12677/ACM.2023.1351090, PDF,   
作者: 陶 艳：青岛大学附属医院心脏超声科，山东 青岛
关键词: 主动脉夹层；铁死亡；生物信息学；关键基因；Aortic Dissection； Ferroptosis； Bioinformatics； Key Genes
摘要: 目的：生信分析结合组织验证以鉴定主动脉夹层(aortic dissection, AD)中的关键铁死亡基因。方法：Limma筛选正常主动脉和AD主动脉间的差异表达基因(differentially expressed genes, DEGs)。基因本体论(gene ontology, GO)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)富集分析预测DEGs在AD中的功能和代谢过程。DEGs与铁死亡相关基因(ferroptosis-related genes, FRGs)数据库FerrDB取交集得到差异表达的铁死亡相关基因(differentially expressed ferrop-tosis-related genes, DEFRGs)。构建AD小鼠模型，验证前4个DEFRGs。结果：正常主动脉样本和AD主动脉样本间存在774个DEGs。DEGs与酶活性、细胞亚结构及糖脂代谢等相关。DEGs与FerrDB数据库交集出17个DEFRGs。通过构建AD小鼠模型，进一步鉴定了DEFRGs中的前4个关键基因，它们分别是雷帕霉素靶蛋白，Mammalian Target of Rapamycin (MTOR)、脂质运载蛋白2，Lipocalin-2 (LCN2)、DNA损伤诱导转录因子4，DNA damage-inducing transcription factor 4 (DDIT4)和淋巴特异性解旋酶，Lymphoid-specific helicase (HELLS)。其中MTOR、LCN2在AD小鼠主动脉中上调，DDIT4在AD小鼠主动脉中下调而HELLS在AD小鼠主动脉和正常主动脉间无变化。结论：铁死亡是AD发展中必不可少的病理过程之一，一些DEFRGs通过介导细胞铁死亡来影响AD的进展。这一发现更深入地认识了AD的致病机制和分子靶点。
Abstract: Objective: To identify the key ferroptosis genes in aortic dissection (AD) by bioinformatics analysis combined with tissue validation. Methods: Limma screened differentially expressed genes (DEGs) between normal aorta and AD aorta. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Ge-nomes (KEGG) enrichment analysis were used to predict the potential functions and metabolic pro-cesses of DEGs in AD. Differentially expressed ferroptosis-related genes (DEFRGs) were determined by intersection of DEGs and FerrDB, which is a database of ferroptosis-related genes (FRGs). AD mouse models were constructed to validate the first four DEFRGs. Results: The analysis indicated that there were 774 DEGs between normal aortic samples and AD aortic samples. DEGs were related to enzyme activity, cell substructure and glucose and lipid metabolism. Seventeen DEFRGs were obtained by intersectional analysis of DEGs and FerrDB database. By constructing an AD mouse model, we further identified the top four key genes in DEFRGs. They are Mammalian Target of Ra-pamycin (MTOR), Lipocalin-2 (LCN2) and DNA damage inducing transcription factor 4 (DDIT4) and Lymphoid-specific helicase (HELLS). Among them, MTOR and LCN2 were up-regulated in AD mouse aorta, DDIT4 was down-regulated in AD mouse aorta, while HELLS had no change between AD mouse aorta and normal aorta. Conclusion: These results suggested that ferroptosis is one of the essential pathological processes in AD and that several DEFRGs affect the progression of AD by me-diating cell ferroptosis. This finding provides deeper insights into the pathogenesis and molecular targets of AD.
文章引用：陶艳. 鉴定主动脉夹层中的关键铁死亡基因[J]. 临床医学进展, 2023, 13(5): 7799-7808. https://doi.org/10.12677/ACM.2023.1351090

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