Disorders in angiogenesis and redox pathways are main factors contributing to the progression of rheumatoid arthritis: A comparative proteomics study

Abstract

Objective. To clarify the pathogenesis of rheumatoid arthritis (RA) by comparing protein expression in fibroblast-like synoviocytes (FLS) from patients with RA with that in FLS from normal subjects, using proteomics analysis.Methods. Proteins extracted from primary cultures of FLS obtained from 50 patients with RA and 10 normal subjects were analyzed by automated 2-dimensional nano-electrospray ionization liquid chromatography tandem mass spectometry. Differentially expressed proteins were screened by 2-sample t-test (P < 0.05) and fold change ( Results. According to the criteria of having >1 unique peptide per protein present and a false discovery rate of <5%, 1,060 proteins were identified from patients with RA, and 1,292 proteins were identified from normal subjects, from which 100 differentially expressed proteins were screened out from the RA proteins. Of these, 46 proteins were up-regulated, and the remaining 54 proteins were down-regulated. Gene ontology and pathway analyses showed that 6 vasculature development-related proteins were up-regulated, including Thy-1, CTGF, and TSP-1, while 11 redox-related proteins were down-regulated, including SOD2. The results were consistent with those obtained using mass spectrometry. Thy-1, VEGF, CTGF, and TSP-1 were down-regulated after Thy-1 knockdown, and VEGF and CTGF were down-regulated after CTGF knockdown. Recombinant human CTGF could enhance proliferation and Transwell migration of human umbilical vein endothelial cells.Conclusion. Up-regulation of vasculature development-related proteins and down-regulation of redox-related proteins in FLS are predominant factors that may contribute to the pathogenesis of RA.

Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21

“…Not unexpectedly, the FoxP3/RORc ratio in the inactive RA groups was the highest while that in the active RA groups was the lowest (figure 1F). We used the Disease Activity Score 28 (DAS28) to explore the relationship between disease activity of RA21 and the FoxP3/RORc ratio. Inverse correlation of the FoxP3/RORc ratio and the DAS28 was observed with r=−0.78, p<0.0001 (figure 1G).…”

Quantitative Proteomics Approach to Screening of Potential Diagnostic and Therapeutic Targets for Laryngeal Carcinoma

“…In addition, using SELDI-TOF-MS method to identify the proteomic shift in laryngeal carcinoma serum, Cheng et al and Liu group reported different findings and conclusions that few proteins were found to vary in concert, and the discrepancies might be due to their technical problems such as varying ability of mass spectrometry to identify a particular protein [14], [15]. Thus, successful application of proteomic technologies to biomedical and clinical research is leading to the discovery of disease-specific biomarkers for diagnosis and treatment monitoring, providing insight into the underlying pathologies and allowing identification of novel therapeutic targets [12]. In the current study, we used 2 chromatographic methods coupled with MS to detect differentially expressed proteins and thereby greatly raised the number of detectable proteins.…”

“…All MS/MS spectrums were identified by using SEQUEST [v.28 (revision 12), Thermo Electron Corp.] against the human UniProtKB/Swiss-Prot database (Release 2011_12_14, with 20249 entries), as previously described [12]. To reduce false positive identification results, a decoy database containing the reverse sequences was appended to the database.…”

“…The two dimensional liquid chromatography tandem MS (2D LC-MS/MS) analysis is emerging as one of the more powerful quantitative proteomics methodologies in the search for tumour biomarkers [10], [11]. For instance, in previous study the authors used 2D LC-MS/MS to identify 100 differentially expressed proteins from rheumatoid arthritis patients, and concluded that up-regulation of vasculature development related proteins and down-regulation of redox-related proteins in fibroblast-like synoviocytes were predominant factors that may contribute to the pathogenesis of rheumatoid arthritis [12]. Moreover, using LC-MS/MS, Moon et al efficiently quantified the proteins of balding and non-balding dermal papilla cells (DPCs) from patients, and 128 up-regulated and 12 down-regulated proteins among 690 distinct proteins were identified in balding DPCs compared to non-balding DPCs [13].…”

10-Hydroxy-2-decenoic acid inhibiting the proliferation of fibroblast-like synoviocytes by PI3K–AKT pathway

“…This study was approved by the local research ethics committee, with informed consent from all the participants concerned. Synovial tissue was isolated enzymatically and primary cultured according to the method previously described [25]. All FLS cells of passages 3-5 were used for the experiment.…”