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Synovial tissue quantitative proteomics analysis reveals paeoniflorin decreases LIFR and ASPN proteins in experimental rheumatoid arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is a common worldwide public health problem, which causes a chronic, systemic inflammatory disorder of synovial joints. Paeoniflorin (PA) has achieved positive results to some extent for the treatment of RA.This study aimed to reveal the potential druggable targets of PA in an experimental RA model using quantitative proteomics analysis.Thirty Sprague-Dawley rats were randomly divided into a normal group, model group and PA group. PA (1 mg/kg) was used to treat collagen-induced arthritis (CIA) rats for 42 days. We used isobaric tags for relative and absolute quantitation-based quantitative proteomics to analyze the synovial tissue of rats. Ingenuity pathway analysis (IPA) software was applied to process the data. The proteins that were targeted via IPA software were verified by Western blots.We found that PA caused 86 differentially expressed proteins (?1.2-fold or ?0.84-fold) compared with the CIA group. Of these varied proteins, 20 significantly changed (p<0.05) proteins referred to 41 CIA-relative top pathways after IPA pathway analysis. Thirteen of the PA-regulated pathways were anchored, which intervened in 24 biological functions. Next, network analysis revealed that leukemia inhibitory factor receptor (LIFR) and asporin (ASPN), which participate in two significant networks, contributed the most to the efficacy of PA treatment. Additionally, Western blots confirmed the aforementioned druggable targets of PA for the treatment of RA.The results reveal that PA may treat RA by decreasing two key proteins, LIFR and ASPN. Our research helps to identify potential agents for RA treatment.

SUBMITTER: Yang S

PROVIDER: S-EPMC5844255 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Synovial tissue quantitative proteomics analysis reveals paeoniflorin decreases LIFR and ASPN proteins in experimental rheumatoid arthritis.

Yang Shu S Xing Zhihua Z Liu Tao T Zhou Jing J Liang Qinghua Q Tang Tao T Cui Hanjin H Peng Weijun W Xiong Xingui X Wang Yang Y

Drug design, development and therapy 20180306

<h4>Background</h4>Rheumatoid arthritis (RA) is a common worldwide public health problem, which causes a chronic, systemic inflammatory disorder of synovial joints. Paeoniflorin (PA) has achieved positive results to some extent for the treatment of RA.<h4>Purpose</h4>This study aimed to reveal the potential druggable targets of PA in an experimental RA model using quantitative proteomics analysis.<h4>Study design and methods</h4>Thirty Sprague-Dawley rats were randomly divided into a normal grou ...[more]

PMID: 29551890

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Project description:BackgroundDifferential diagnosis among psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (Abneg RA) can be challenging particularly in the clinical setting of peripheral phenotype and autoantibodies seronegativity. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and Abneg RA and test their predictive value of therapeutic response.MethodsThirty-four PsA patients [12 DMARD naive and 22 non-responder to methotrexate (MTX-IR)] with peripheral joint involvement and 55 Abneg RA (27 DMARD naive and 28 MTX-IR) underwent US-guided ST biopsy and immunohistochemistry (IHC) for CD68+, CD3+, CD20+, CD21+, CD117+, and CD138+ cells. After study entry, each DMARD-naive patient started MTX therapy and was followed in an outpatient setting for at least 6 months to define the achievement of Minimal Disease Activity (PsA) and DAS remission (Abneg RA) status respectively. Each IR-MTX patient was treated according to EULAR recommendations.ResultsAt study entry, IHC analysis revealed that PsA patients had comparable levels of lining and sublining CD68+ and sublining CD21+, CD20+, and CD3+ cells than Abneg RA, despite the therapeutic regimen. Moreover, regardless of the therapeutic scheme, PsA patients showed higher IHC score of CD117+ cells (p = 0.0004 and p = 0.0005 for naive and MTX-IR patients respectively) compared to Abneg RA patients. Conversely, Abneg RA patients showed higher IHC score of CD138+ cells, irrespective to the therapeutic scheme (p = 0.04 and p = 0.002 for naive and MTX-IR patients respectively). Analyzing the response rate to the therapeutic scheme, naive PsA patients reaching MDA status at 6 months follow-up, showed, at the study entry, lower IHC score of CD3+ cells compared to PsA patients not reaching this outcome (p = 0.02); conversely, naive Abneg RA patients reaching DAS remission status at 6 months follow-up, showed, at the study entry, lower IHC score of sublining CD68+ cells compared to Abneg RA patients not reaching this outcome (p < 0.001).ConclusionsCD117+ and CD138+ cells are differentially distributed among PsA and Abneg RA. Histological analysis of ST may help to solve the clinical overlap between the two diseases and provides prognostic data about the therapy success.

Dataset Information

Synovial tissue quantitative proteomics analysis reveals paeoniflorin decreases LIFR and ASPN proteins in experimental rheumatoid arthritis.

Publications

Synovial tissue quantitative proteomics analysis reveals paeoniflorin decreases LIFR and ASPN proteins in experimental rheumatoid arthritis.

Similar Datasets

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