J Rheum Dis.  2011 Jun;18(2):101-109.

Study of the Gene Expressions in Rheumatoid Arthritis Synovial Macrophages Using Network Analysis

• Ji JD
• Kim TH
• Lee B
• Choi SJ
• Lee YH
• Song GG

Abstract

OBJECTIVE
We wanted to investigate the mechanisms that could account for the pathogenesis of rheumatoid arthritis, so we examined the different expressions of the genes in rheumatoid arthritis (RA) synovial fluid macrophages as compared with that of normal peripheral blood (PB) monocyte-derived macrophages using microarray and bioinformatic analysis.
METHODS
We examined the expression of genes by using a gene expression oligonucleotide microarray. The differences of the gene expressions between the RA synovial macrophages and the normal PB monocytes-derived macrophages were analyzed using bioinformatic tools, including cytoscape and its plugin.
RESULTS
In this study, we found that 899 genes (464 genes up-regulated and 435 genes down-regulated) were differentially expressed between the two groups. Among the 899 genes, 552 genes were included for gene ontology analysis and network analysis. Based on biological process ontology, they were categorised mainly into immune response processes, responses to stimulus and signaling and regulation of biological processes. In addition to the genes related with STAT1 and AP-1 signaling, we found that the genes involved in the antigen processing and the cell cycle are abundantly expressed in RA synovial macrophages, suggesting that these genes may play an important role in the pathogenesis of RA.
CONCLUSION
Our study suggest that this approach using integration of the gene expression profile with the protein interaction data may help to find several important pathogenic mechanisms in RA.

Keyword

Rheumatoid arthritis; Synovial macrophages; Microarray; Bioinformatics

MeSH Terms

Antigen Presentation
Arthritis, Rheumatoid
Biological Processes
Cell Cycle
Computational Biology
Gene Expression
Genes, vif
Macrophages
Oligonucleotide Array Sequence Analysis
Synovial Fluid
Transcription Factor AP-1
Transcriptome
Transcription Factor AP-1

Figure

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  Figure 1. Overview of the bioinformatic analysis using cytoscape.

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  Figure 2. The array data for the gene expressions was validated by performing quantitative real-time PCR in the healthy volunteer PB monocyte-derive macrophages and the RA synovial macrophages ∗p<0.05 versus the healthy volunteer PB monocyte-derive macrophages.

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  Figure 3. (A) Map of the biological processes associated with RA synovial macrophages. Darker nodes mean the more significant ontology terms. The size is proportional to the number of genes included in that ontology term. (B) Network of the genes included in the immune system processes (GO. 2376). A blue node means down-regulation of genes and a red node means upregulation of genes in the RA synovial macrophages.

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  Figure 4. Different expressions of the STAT1-related genes in the RA synovial macrophages. A blue node means down-regulation of genes and a red node means upregulation of genes in the RA synovial macrophages.

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  Figure 5. (A) Detection of densely connected regions in the network of genes differentially expressed in the RA synovial macrophages and the PB monocyte-derived macrophages from healthy volunteer using MCODE. A square node is a seed node. (B) Identification of the functional modules as highly connected regions with similar responses using jActiveModules. A blue node means down-regulation of genes and a red node means upregulation of genes in the RA synovial macrophages.

Reference

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