Huang Yiyong,Yang Ge,Liu Yaoxi,et al.Proteomic analysis of serum-derived exosomes from congenital pseudarthrosis of tibia[J].Journal of Clinical Pediatric Surgery,2022,21(06):551-557.[doi:10.3760/cma.j.cn101785-202102043-010]
基于生物信息学分析的先天性胫骨假关节血清来源外泌体蛋白质组学研究
- Title:
- Proteomic analysis of serum-derived exosomes from congenital pseudarthrosis of tibia
- Keywords:
- Congenital Pseudarthrosis of Tibia; Tibia/AB; Pseudarthrosis/CN; Proteomics/CL; Proteomics/MT; Exosomes
- 摘要:
- 目的 比较先天性胫骨假关节（congenital pseudarthrosis of tibia，CPT）和正常儿童血清外泌体中蛋白的表达差异，寻找CPT的可能致病机制。方法 收集湖南省儿童医院6例CPT患儿和4例正常儿童的静脉血，通过分离出静脉血清、提取血清外泌体，使用串联质谱标签（tandem mass tag，TMT）标记定量蛋白组学技术，确定CPT患儿和正常儿童血清外泌体中的差异表达蛋白，并对差异蛋白进行GO分析、KEGG分析、DisGeNET富集分析及PPI分析。结果 与正常儿童血清中外泌体蛋白相比，CPT来源的血清外泌体中表达上调的蛋白共121个，表达下调的蛋白共289个。KEGG分析结果显示，差异蛋白在补体系统富集最为显著；糖代谢在GO分类中的生物进程中富集；DisGeNET富集分析结果显示，排名前五的疾病中有3种和骨质疏松症有关；PPI富集分析结果显示糖代谢为差异蛋白富集模块之一。结论 补体系统紊乱和细胞能量代谢异常可能是CPT的潜在致病机制。本研究为探索先天性胫骨假关节的病因及发病机制提供了新的思路。
- Abstract:
- Objective To explore the possible pathogenesis of congenital pseudarthrosis of tibia (CPT) through compare the differential protein expression in serum-derived exosomes (SDEs) between CPT and normal children.Methods SDEs were extracted from venous plasma of 6 CPT children and 4 normal controls.Then differentially expressed proteins were examined by tandem mass tag (TMT)-based proteomics.And proteomic information was acquired through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, gene ontology (GO) classification, DisGeNET enrichment analysis and protein-protein interaction (PPI) enrichment analysis.Results Based upon proteomics analysis, 121 up-regulated and 289 down-regulated proteins were identified.Complement & coagulation cascade was the most obvious enrichment in KEGG pathway.Monosaccharide metabolic process was one of enriched process during the biological process of gene ontology (GO) classification.DisGeNET enrichment analysis indicated that three of top five diseases were associated with osteoporosis.And glycolysis/gluconeogenesis was a part of enriched terms during PPI enrichment analysis.It hinted that complement and glycolysis/gluconeogenesis were abnormal in CPT.Conclusion Abnormality of complement and glycolysis/gluconeogenesis might be a potential pathogenic mechanism of CPT.Also this study may provide new rationales for exploring the etiology and pathogenesis of CPT.
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备注/Memo
收稿日期:2021-02-14。
基金项目:湖南省重点研发计划（2020SK2113）；湖南省儿童肢体畸形临床医学研究中心（2019SK4006）；湖南省出生缺陷协同防治科技重大专项（2019SK1010）
通讯作者:梅海波,Email:meihaibo@sohu.com