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




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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-1α pathway on catabolism was detected by HIF-1α 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-1α 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-1α 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.



Autor: Xin Yu Yang , Kai Di Zheng , Ke Lin , Guifeng Zheng, Hai Zou, Jian Min Wang, Yao Yao Lin, Chifundo Martha Chuka, Ren Shan Ge, Wei

Fuente: http://plos.srce.hr/



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