Exploring the role of monocyte chemoattractant protein-1 in fibroblast-like synovial cells in rheumatoid arthritis

Author:

Tong Xiang1,Yu Dongdong1,Yu Li2,Chen Weiqian3,Wen Yanling3,Gu Pengcheng1

Affiliation:

1. Department of Orthopedic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

2. Operating Room, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

3. Department of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

Abstract

Background Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease with persistent synovitis. In the present study, the impact of monocyte chemoattractant protein-1 (MCP-1) was explored to determine methods for the diagnosis and treatment of RA. Methods First, fibroblast-like synoviocytes (FLSs) were obtained from a collagen-induced rat RA model. Next, MCP-1-overexpression plasmid and small interfering RNA were transfected into human and rat FLSs. Cell Counting Kit-8 (CCK-8), Transwell migration and flow cytometry assays were used to analyze cell proliferation, migration and apoptosis of FLSs following MCP-1 transfections, respectively. Furthermore, western blotting was used to analyze the expression levels of p-P38, p-PI3K, PI3K, CD31, VEGF, TNF-α and IL-β in FLSs following MCP-1 transfection. In addition, reverse transcription-quantitative PCR and ELISAs were used to analyze the expression levels of C-reactive protein (CRP), estrogen receptor, MCP-1 and pentraxin-3 in patients with clinical RA, followed by correlation analysis of clinical data. Finally, expression validation, diagnostic and protein-protein interaction (PPI) network analysis of MCP-1 were performed. Results MCP-1 promoted FLS proliferation and migration, and affected the apoptosis of FLSs. In addition, the expression levels of p-P38, p-PI3K, PI3K, CD31, VEGF, TNF-α and IL-β were also affected by MCP-1. In patients with clinical RA, the expression level of MCP-1 was increased. Moreover, CRP expression level was significantly up-regulated in RA. Clinically, MCP-1 was strongly correlated with tender joint count, swollen joint count, visual analog scale for general health and disease activity score 28 (DAS28)-MCP-1, and was moderately correlated with DAS28 and DAS28-CRP. PPI analysis showed that MCP-1 mainly interacted with other inflammatory cytokines. Conclusion In conclusion, MCP-1 may play a significant regulatory role in RA, and could be used as a measurement index of clinical RA activity.

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference50 articles.

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