Proteomics analysis indicates the involvement of immunity and inflammation in the onset stage of SOD1-G93A mouse model of ALS
Proteomics analysis indicates the involvement of immunity and inflammation in the onset stage of SOD1-G93A mouse model of ALS
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DOI：
10.1016/j.jprot.2022.104776
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发表时间：
2022-11-29
影响因子：
3.3
通讯作者：
Guo, Yansu
中科院分区：
文献类型：
--
作者：
Chen, Lin;Wang, Ningyuan;Guo, Yansu
肌萎缩侧索硬化症（amyotrophiclateralsclerosis，ALS）是一种致死性运动神经元退行性疾病，其发病机制尚不清楚。我们基于4D无标记定量蛋白质组学（4D-LFQ）和液相色谱-串联质谱（LC-MS/MS）分析了SOD 1-G93 A转基因小鼠发病期和同窝非转基因（NTG）小鼠脊髓中差异表达的蛋白质（DEPs）。在我们的研究中，筛选了189个DEP，其中166个上调，23个下调。进行了同源群（COG）/真核同源群（KOG）分类、亚细胞定位注释、基因本体（GO）和京都基因和基因组百科全书（KEGG）途径富集、聚类分析和蛋白质-蛋白质相互作用（PPI）网络分析。平行反应监测（PRM）分析验证了KEGG免疫和炎症相关途径的48个蛋白。DEPs主要参与补体和凝血级联反应、抗原加工和呈递、NF-κ B B信号通路、视黄酸诱导基因I（RIG）-I样受体信号通路、细胞外基质-受体（ECM -receptor）相互作用、粘着斑、吞噬体和溶酶体等信号通路。PPI网络分析确定Fn 1、Fga、Ser-pina 1 e和Serpina 3 n为潜在的生物标志物。我们的发现拓宽了视野，扩大了我们对ALS中免疫和炎症的理解。意义：本研究全面描述了发病期SOD 1-G93 A小鼠脊髓蛋白质组学中的DEPs。与以往的进展期研究相比，我们发现免疫和炎症在ALS的发病阶段起着重要作用。PRM验证的几种途径为ALS的病理机制带来了新的见解。RIG-I-like信号通路在ALS中的参与以及潜在的生物标志物Fga、Fn 1、Serpina 1 e和Serpina 3 n是对现有知识的补充。
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disease, and the pathogenic mechanism that underlies ALS is still unclear. We analyzed the differentially expressed proteins (DEPs) in the spinal cord between SOD1-G93A transgenic mice at the onset stage and non-transgenic (NTG) littermates based on 4D label -free quantitative proteomics (4D-LFQ) with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In our study, 189 DEPs were screened, of which 166 were up-regulated and 23 down-regulated. Clusters of Orthologous Groups (COG)/ EuKaryotic Orthologous Groups (KOG) classification, subcellular localization annotation, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, clustering analysis and protein-protein interaction (PPI) network analyses were performed. Parallel reaction monitoring (PRM) analysis validated 48 proteins from immunity and inflammation-related pathways of KEGG. We described the function and distribution of DEPs, most of which were involved in the following pathways: complement and coagulation cascades, antigen processing and presentation, NF-kappa B signaling pathway, Retinoic acid-inducible gene I (RIG)-I-like receptor signaling pathway, the extracellular matrix-receptor (ECM -receptor) interaction, focal adhesion, phagosome and lysosome. PPI network analysis identified Fn1, Fga, Ser-pina1e and Serpina3n as potential biomarkers. Our discoveries broaden the view and expand our understanding of immunity and inflammation in ALS.Significance: This study gives a comprehensive description of DEPs in the spinal cord proteomics of SOD1-G93A mice at the onset period. Compared with a previous study focusing on progressive stage, we showed that im-munity and inflammation play an important role at the onset stage of ALS. Several pathways validated by PRM bring new insight to the pathological mechanisms of ALS. The participation of RIG-I-like signaling pathway in ALS and potential biomarkers Fga, Fn1, Serpina1e and Serpina3n are supplements to existing knowledge.