Abstract

BackgroundThe purpose of this study is to identify key genes and microRNAs (miRNAs) involved in autoantibody-mediated arthritis (AMA).MethodsA time-course microarray data (ID: GSE27492) of peripheral blood leukocytes, ankle tissue, and synovial fluid from K/BxN mouse serum-transferred mice were downloaded from Gene Expression Omnibus. Those samples were collected at days 0, 1, 3, 7, 12, and 18 after serum injection. Limma of R was employed to identify differentially expressed genes (DEGs) in samples collected at days 1–18 compared with those collected at day 0. Consistent DEGs were obtained by taking the interaction of DEGs from different time points, followed by functional enrichment analysis. MiRNAs were screened out and constructed into regulatory network with DEGs using Cytoscape.ResultsIn total, 17 consistent DEGs were obtained, including downregulated Ephx1 and upregulated AF251705, Adam8, Arg1, Basp1, Ccl2, Ccl7, Ccl9, Ccr2, Clec4a2, Clec4d, Cxcl1, Fabp5, Fcgr1, Gp49a, Il1rn, and Saa3. Those DEGs were associated with biological processes of immune response, inflammatory response, and defense response; chemokine signaling pathway; cytokine-cytokine receptor interaction; and NOD-like receptor signaling pathway. Additionally, 202 miRNAs were identified to have a regulatory effect on 9 of the 17 DEGs. Notably, miR-944, miR-374a, and miR374b were found to regulate the expression of Cxcl1, Ccl7, and Ccl2. Clec4d was targeted by 78 miRNAs.ConclusionsOur study reveals that 17 DEGs and 202 miRNAs may be associated with autoimmune disorder in the progression of AMA, which could guide future researches.

Highlights

  • The purpose of this study is to identify key genes and microRNAs involved in autoantibodymediated arthritis (AMA)

  • The K/BxN mouse model of arthritis is a common AMA mouse model, in which the upstream adaptive immune response involved in generation of arthritogenic

  • Identification of differentially expressed genes (DEGs) Compared with the samples collected at day 0 after K/BxN serum injection, a total of 0, 35, 103, 62, and75 DEGs were separately obtained from the samples collected at day 1, 3, 7, 12, and 18

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Summary

Introduction

The purpose of this study is to identify key genes and microRNAs (miRNAs) involved in autoantibodymediated arthritis (AMA). Inflammatory response and immune response are found to play critical roles in the pathogenesis of RA [2,3,4]. Matrix metalloproteinases (MMPs) play key roles in the destructive process and are implicated in arthritis [9], especially MMP-1 and MMP-13. Those uncovered genes demonstrate an involvement of the gene factor in the progression of arthritis. The K/BxN mouse model of arthritis is a common AMA mouse model, in which the upstream adaptive immune response involved in generation of arthritogenic

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