Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
MicroRNA and mRNA Integrated Analysis in Rheumatoid Arthritis Synovial Macrophages.
Ji3, Jong Dae, Lee5, Bit-Na-Ra, Kim5, Tae-Hwan, Jun5, Jae-Bum, Yoo5, Dae-Hyun, Na2, Kyung-Sun, Woo4, Jin-Hyun
Department of Biochemistry, College of Medicine, Korea University, Seoul, Korea
Kim's Clinic, Seoul, Korea
Rheumatology, College of Medicine, Korea University, Seoul, Korea, Republic of
Rheumatology, College of Medicine, Korea University, Seoul, Korea
The Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea
Dysregulated expression of microRNAs (miRNAs) has been shown to be a hallmark of human diseases, and recent studies provide growing evidences that miRNA dysregulation might be play important roles in the pathogenesis of rheumatoid arthritis. Abnormal expression of certain miRNAs was found in peripheral blood mononuclear cells, synovial fibroblasts and synovial tissue from patients with rheumatoid arthritis. To investigate whether abnormal expression of miRNA in rheumatoid arthritis could account for dysregulated expression of certain genes, we compared different expressions of miRNAs and mRNAs in rheumatoid synovial fluid macrophages to normal peripheral blood monocytes, using gene expression oligonucleotide microarray and microRNA microarray.
Comparative analysis of mRNA profiles showed significant different expressions (defined as 2-fold change and P<0.05) of 430 genes in RA synovial macrophages, of which 303 (70%) were upregulated and 127 (30%) were downregulated, compared to normal PB monocytes. Among the biological process class, highly represented genes included those involved in cell adhesion, immunity and defense, nucleic acid metabolism and signal transduction. Among molecular function class, highly represented genes included those involved in cell adhesion molecule, defense/immunity protein, receptor, nucleic acid binding and transcription factor. We identified 13 differentially expressed miRNAs in RA synovial macrophages, compared with normal PB monocytes. Out of 13 miRNAs, 9 miRNAs were upregulated and 4 miRNAs were downregulated in RA synovial macrophages. Total 62 genes were predicted as target genes of 13 differentially expressed miRNAs in RA synovial macrophages. Out of these 62 genes, 28 genes were upregulated and 34 genes were downregulated. Among 62 miRNA-targeted dysregulated genes, few genes such as GSTM1, VIPR1, PADI4, CDA, IL21R, CCL5, IL7R, STAT4, HTRA1 and IL18BP have been reported to be associated with rheumatoid arthritis. We validated the differential expression of these genes in RA synovial macrophages using quantitative real time PCR.
In the present study, we observed that several miRNAs are differentially expressed in RA synovial macrophages, and suggest that these dysregulated miRNAs may regulate expressions of several genes associated with the pathogenesis of RA.
To cite this abstract, please use the following information:
Ji, Jong Dae, Lee, Bit-Na-Ra, Kim, Tae-Hwan, Jun, Jae-Bum, Yoo, Dae-Hyun, Na, Kyung-Sun, et al; MicroRNA and mRNA Integrated Analysis in Rheumatoid Arthritis Synovial Macrophages. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :359