Energy Metabolism Disorder as a Contributing Factor of Rheumatoid Arthritis: A Comparative Proteomic and Metabolomic Study

doi:10.1371/journal.pone.0132695

科研成果详情

题名	Energy Metabolism Disorder as a Contributing Factor of Rheumatoid Arthritis: A Comparative Proteomic and Metabolomic Study
作者	Yang, Xin Yu 1; Zheng, Kai Di 2; Lin, Ke 2; Zheng, Guifeng 2; Zou, Hai 2; Wang, Jian Min 3; Lin, Yao Yao 2; Chuka, Chifundo Martha 2; Ge, Ren Shan 2; Zhai, Weitao 4; Wang, Jian Guang 2
发表日期	2015-07-06
发表期刊	PLOS ONE 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	SYNOVIAL-FLUID ; HYPOXIA ; ANGIOGENESIS ; PATHOGENESIS ; PROFILES
摘要	Objectives To explore the pathogenesis of rheumatoid arthritis (RA), the different metabolites were screened in synovial fluid by metabolomics. Methods Synovial fluid from 25 RA patients and 10 normal subjects were analyzed by GC/TOF MS analysis so as to give a broad overview of synovial fluid metabolites. The metabolic profiles of RA patients and normal subjects were compared using multivariate statistical analysis. Different proteins were verified by qPCR and western blot. Different metabolites were verified by colorimetric assay kit in 25 inactive RA patients, 25 active RA patients and 20 normal subjects. The influence of hypoxia-inducible factor (HIF)-1 alpha pathway on catabolism was detected by HIF-1 alpha knockdown. Results A subset of 58 metabolites was identified, in which the concentrations of 7 metabolites related to energy metabolism were significantly different as shown by importance in the projection (VIP) (VIP >= 1) and Student's t-test (p<0.05). In the 7 metabolites, the concentration of glucose was decreased, and the concentration of lactic acid was increased in the synovial fluid of RA patients than normal subjects verified by colorimetric assay Kit. Receiver operator characteristic (ROC) analysis shows that the concentration of glucose and lactic acid in synovial fluid could be used as dependable biomarkers for the diagnosis of active RA, provided an AUC of 0.906 and 0.922. Sensitivity and specificity, which were determined by cut-off points, reached 84% and 96% in sensitivity and 95% and 85% in specificity, respectively. The verification of different proteins identified in our previous proteomic study shows that the enzymes of anaerobic catabolism were up-regulated (PFKP and LDHA), and the enzymes of aerobic oxidation and fatty acid oxidation were down-regulated (CS, DLST, PGD, ACSL4, ACADVL and HADHA) in RA patients. The expression of HIF-1 alpha and the enzymes of aerobic oxidation and fatty acid oxidation were decreased and the enzymes of anaerobic catabolism were increased in FLS cells after HIF-1 alpha knockdown. Conclusion It was found that enhanced anaerobic catabolism and reduced aerobic oxidation regulated by HIF pathway are newly recognized factors contributing to the progression of RA, and low glucose and high lactic acid concentration in synovial fluid may be the potential biomarker of RA.
资助项目	Natural Science Foundations; Health Bureau funding of Zhejiang Province [R13H060001, LY12H28003, 2012KYB123, 2013KYB170]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81201375, 81472055]; Zhejiang College Student Innovative Research Team [2015R413064]
出版者	PUBLIC LIBRARY SCIENCE
出版地	SAN FRANCISCO
ISSN	1932-6203
卷号	10 期号:7 页码:e0132695.
DOI	10.1371/journal.pone.0132695
页数	15
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
WOS记录号	WOS:000358157600312
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	26147000
PMC记录号	PMC4492520
SCOPUSEID	2-s2.0-84940201998
通讯作者地址	[Zhai, Weitao]Shanghai Guanghua Special Hosp Rheumatoid Arthrit, Dept Orthopaed Surg, Shanghai, Peoples R China.
Scopus学科分类	Multidisciplinary
引用统计	被引频次：62[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/17343
专题	药学院（分析测试中心）检验医学院（生命科学学院、生物学实验教学中心）_生物化学与分子生物学系
通讯作者	Zhai, Weitao
作者单位	1.Wenzhou Med Univ, Sch Pharmaceut Sci, Dept Med Chem, Wenzhou, Peoples R China; 2.Wenzhou Med Univ, Sch Basic Med Sci, Dept Biochem, Wenzhou, Peoples R China; 3.Jiamusi Cent Hosp, Dept Rheumatol, Jiamusi, Peoples R China; 4.Shanghai Guanghua Special Hosp Rheumatoid Arthrit, Dept Orthopaed Surg, Shanghai, Peoples R China
第一作者单位	药学院（分析测试中心）
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Yang, Xin Yu,Zheng, Kai Di,Lin, Ke,et al. Energy Metabolism Disorder as a Contributing Factor of Rheumatoid Arthritis: A Comparative Proteomic and Metabolomic Study[J]. PLOS ONE,2015,10(7):e0132695..
APA	Yang, Xin Yu., Zheng, Kai Di., Lin, Ke., Zheng, Guifeng., Zou, Hai., ... & Wang, Jian Guang. (2015). Energy Metabolism Disorder as a Contributing Factor of Rheumatoid Arthritis: A Comparative Proteomic and Metabolomic Study. PLOS ONE, 10(7), e0132695..
MLA	Yang, Xin Yu,et al."Energy Metabolism Disorder as a Contributing Factor of Rheumatoid Arthritis: A Comparative Proteomic and Metabolomic Study".PLOS ONE 10.7(2015):e0132695..