与肌少症发病相关的线粒体自噬靶点基因筛选及其在骨骼肌组织中表达观察

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中文摘要：目的基于GEO数据库数据筛选与肌少症发病相关的线粒体自噬靶点基因，并观察其在肌少症患者骨骼肌组织中的表达变化。方法从GEO数据库检索肌少症的基因图谱数据，筛选肌少症发病的差异表达基因。从GeneCard数据库中检索并收集线粒体自噬相关基因。使用"VennDiagram"包将肌少症发病的差异表达基因与线粒体自噬相关基因取交集，得到与肌少症发病相关的线粒体自噬差异表达基因。运用基因本体论(GO)和京都基因与基因百科全书(KEGG)通路富集分析与肌少症发病相关的线粒体自噬差异表达基因的生物学功能，通过Cytoscape软件筛选与肌少症发病相关的线粒体自噬靶点基因，观察GSE136344基因表达图谱中肌少症、健康对照者骨骼肌与肌少症发病相关的线粒体自噬靶点基因表达情况。结果得到与肌少症发病相关的线粒体自噬差异表达基因99个。与肌少症发病相关的线粒体自噬差异表达基因主要涉及神经变性途径-多种疾病信号通路、帕金森疾病信号通路、朊毒体病信号通路等;主要调控能量代谢、细胞呼吸、氧化磷酸化调节等生物学过程，主要定位于线粒体内膜、线粒体内部的大分子蛋白质复合物等，参与调节跨膜转运活性等分子功能。与肌少症发病相关的线粒体自噬靶点基因有线粒体内膜蛋白基因(IMMT)、动态蛋白1样蛋白基因(DNM1L)及ATP合酶F1亚基α基因(ATP5A1)等;与正常骨骼肌组织相比，肌少症患者骨骼肌组织中IMMT、DNM1L表达低(P均<0。05)。结论与肌少症发病相关的线粒体自噬靶点基因为IMMT、DNM1L。与肌少症发病相关的线粒体自噬靶点基因可通过影响神经变性途径-多种疾病信号通路、帕金森疾病信号通路及朊毒体病信号通路等，参与调控能量代谢、细胞呼吸、氧化磷酸化调节等生物学过程，参与肌少症的发病。肌少症患者骨骼肌组织中IMMT、DNM1L低表达。

外文标题：Screening of hub mitophagy-related genes and their expression in skeletal muscle tissues of patients with sarcopenia

外文摘要：Objective Based on the Gene Expression Omnibus(GEO)database,our aim is to identify potential mi-tophagy-related genes for sarcopenia and to observe their expression changes in skeletal muscle tissues of patients with sarco-penia.Methods Gene expression datasets for sarcopenia(GSE1428)were obtained from the GEO database and differen-tially expressed genes(DEGs)in the sarcopenia samples and normal samples were screened.The DEGs of sarcopenia were intersected with mitophagy-related genes using the"VennDiagram"package to obtain mitophagy-related DEGs of sarcope-nia.The biological functions of mitophagy-related DEGs for sarcopenia were analyzed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG).The mitophagy-related target genes for sarcopenia were selected using Cyto-scape,and the expression changes of these genes in skeletal muscle tissues of patients with sarcopenia and controls were ob-served in the gene expression datasets GSE136344 for sarcopenia.Results Ninety-nine mitophagy-DEGs for sarcopenia were screened out.As shown by KEGG enrichment analyses,these genes were significantly enriched in pathways responsi-ble for neurodegeneration-multiple diseases,Parkinson's disease,prion disease,and so on.GO function annotation showed that DEGs were mostly located in the mitochondrial inner membrane and mitochondrial protein-containing complex,where they were engaged in biological processes such as energy metabolism,cellular respiration,and oxidative phosphorylation.They were also involved in the molecular functions of active transmembrane transporter activity,etc.The inner membrane mitochondrial protein(IMMT),dynamin 1-like(DNM1L),and ATP5A1 were identified as the mitophagy-related target genes for sarcopenia.Sarcopenic patients exhibited lower expression levels of IMMT and DNM1L in their skeletal muscles in comparison with non-sarcopenic individuals(all P<0.05).Conclusions IMMT and DNM1L were identified as signifi-cant mitophagy-related target genes for sarcopenia.These target genes contributed to the pathogenesis of Sarcopenia not on-ly by affecting neurodegeneration-multiple diseases pathways,Parkinson's disease pathway,and prion disease pathway but also by participating in biological processes such as energy metabolism,cellular respiration,and oxidative phosphorylation.Patients with sarcopenia exhibited lower expression levels of IMMT and DNM1L in skeletal muscle tissues.

外文关键词：

mitophagysarcopenianeurodegeneration-multiple diseases pathwayParkinson disease pathwayprion disease pathwayenergy metabolismcellular respirationoxidative phosphorylationinner membrane mitochon-drial proteindynamin 1-like gene

作者：

徐锐、李燕燕、徐红

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作者单位：

新疆维吾尔自治区人民医院老年医学中心,乌鲁木齐 830000

新疆维吾尔自治区人民医院心脏外科

关键词：

线粒体自噬肌少症神经变性途径—多种疾病信号通路帕金森疾病信号通路朊毒体病信号通路能量代谢细胞呼吸氧化磷酸化线粒体内膜蛋白动态蛋白1样蛋白

基金：

新疆维吾尔自治区自然科学基金资助项目

项目编号：

2021D01C163

出版年：

2024

DOI：

10.3969/j.issn.1002-266X.2024.06.011

山东医药

山东卫生报刊社

山东医药

CSTPCD

影响因子：1.225

ISSN：1002-266X

年,卷(期)：2024.64(6)

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