{"title":"Proteome and Metabolome Profiling of Anticoagulant Disorders Induced by Familial Protein S Deficiency","authors":"Caiping Zhang, Yimin Zhang, Binjie Liu, Yongxv Chen, Yue Xie, Huiting Huang, Zhongqiu Liu, Zhuoru He","doi":"10.1021/acs.jproteome.4c00399","DOIUrl":null,"url":null,"abstract":"Protein S deficiency (PSD) is an autosomal dominant disorder characterized by congenital thrombophilia. Studies on PSD are limited yet, resulting in a lack of clarity about molecular changes during abnormal coagulation. Proteomics and metabolomics analyses were conducted on the plasma of PSD patients based on liquid and gas chromatography–mass spectrometry (LC- and GC–MS). Differential proteins and metabolites of PSD were then filtered by univariate statistical analysis and subjected to network analysis using the ingenuity pathway analysis (IPA) platform. The proteome and metabolome of PSD were obviously disturbed, and the biological pathway of coagulation and complement cascades was the most affected. During PSD, overall levels of anticoagulant protein decreased and negative regulation of thrombin production was reduced, causing the formation of fibrin clots and platelet aggregation. Furthermore, 9 differential proteins correlated significantly with protein S, comprising A2M, AGT, APOE, FGG, GPLD1, IGHV1–69, CFHR5, CPN2, and CA1. The biological networks suggested that the pathways of acute phase response, FXR/RXR activation, serotonin receptor signaling, and p70S6K signaling were associated with PSD, indicating an interaction disorder of inflammatory immune and lipid metabolism. The findings may contribute to knowledge of available functional molecules and biological pathways of familial PSD and help with treatment improvement. Data are available via ProteomeXchange with identifier PXD055111 and MetaboLights with reference number MTBLS2653.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Proteome Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1021/acs.jproteome.4c00399","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
Protein S deficiency (PSD) is an autosomal dominant disorder characterized by congenital thrombophilia. Studies on PSD are limited yet, resulting in a lack of clarity about molecular changes during abnormal coagulation. Proteomics and metabolomics analyses were conducted on the plasma of PSD patients based on liquid and gas chromatography–mass spectrometry (LC- and GC–MS). Differential proteins and metabolites of PSD were then filtered by univariate statistical analysis and subjected to network analysis using the ingenuity pathway analysis (IPA) platform. The proteome and metabolome of PSD were obviously disturbed, and the biological pathway of coagulation and complement cascades was the most affected. During PSD, overall levels of anticoagulant protein decreased and negative regulation of thrombin production was reduced, causing the formation of fibrin clots and platelet aggregation. Furthermore, 9 differential proteins correlated significantly with protein S, comprising A2M, AGT, APOE, FGG, GPLD1, IGHV1–69, CFHR5, CPN2, and CA1. The biological networks suggested that the pathways of acute phase response, FXR/RXR activation, serotonin receptor signaling, and p70S6K signaling were associated with PSD, indicating an interaction disorder of inflammatory immune and lipid metabolism. The findings may contribute to knowledge of available functional molecules and biological pathways of familial PSD and help with treatment improvement. Data are available via ProteomeXchange with identifier PXD055111 and MetaboLights with reference number MTBLS2653.
期刊介绍:
Journal of Proteome Research publishes content encompassing all aspects of global protein analysis and function, including the dynamic aspects of genomics, spatio-temporal proteomics, metabonomics and metabolomics, clinical and agricultural proteomics, as well as advances in methodology including bioinformatics. The theme and emphasis is on a multidisciplinary approach to the life sciences through the synergy between the different types of "omics".