Decoy receptor 3 regulates the expression of various genes in rheumatoid arthritis synovial fibroblasts

• Published in: International journal of molecular medicine Vol. 32; no. 4; pp. 910 - 916
• Main Authors: FUKUDA, KOJI, MIURA, YASUSHI, MAEDA, TOSHIHISA, TAKAHASHI, MASAYASU, HAYASHI, SHINYA, KUROSAKA, MASAHIRO
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01-10-2013; Spandidos Publications UK Ltd
• Subjects: Apoptosis; Apoptosis - genetics; Arthritis, Rheumatoid - genetics; Cell Differentiation - genetics; Chromosomes; Cluster Analysis; Data analysis; decoy receptor 3; Down-Regulation; Fas Ligand Protein - genetics; Fas Ligand Protein - metabolism; fibroblast-like synoviocytes; Fibroblasts; Fibroblasts - cytology; Gene expression; gene expression profile; Gene Expression Profiling; Humans; Kinases; Ligands; Metabolism; microarray assay; Motility; Oligonucleotide Array Sequence Analysis; Osteoclasts - metabolism; Pathogenesis; Proteins; Reading; Receptors, Tumor Necrosis Factor, Member 6b - genetics; Receptors, Tumor Necrosis Factor, Member 6b - metabolism; Rheumatoid arthritis; RNA - genetics; RNA polymerase; Signal Transduction; Studies; Synovial Membrane - cytology; Synovial Membrane - metabolism; Synovial Membrane - pathology; Transcriptome; Tumor Necrosis Factor Ligand Superfamily Member 15 - genetics; Tumor Necrosis Factor Ligand Superfamily Member 15 - metabolism; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumors; Up-Regulation; United States > US
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2013.1461

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor (TNF) receptor (TNFR) superfamily, lacks the transmembrane domain of conventional TNFRs in order to be a secreted protein. DcR3 competitively binds and inhibits members of the TNF family, including Fas ligand (FasL), LIGHT and TNF-like ligand 1A (TL1A). We previously reported that TNFα-induced DcR3 overexpression in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) protects cells from Fas-induced apoptosis. Previous studies have suggested that DcR3 acting as a ligand directly induces the differentiation of macrophages into osteoclasts. Furthermore, we reported that DcR3 induces very late antigen-4 (VLA-4) expression in THP-1 macrophages, inhibiting cycloheximide-induced apoptosis and that DcR3 binds to membrane-bound TL1A expressed on RA-FLS, resulting in the negative regulation of cell proliferation induced by inflammatory cytokines. In the current study, we used cDNA microarray to search for genes in RA-FLS whose expression was regulated by the ligation of DcR3. The experiments revealed the expression profiles of genes in RA-FLS regulated by DcR3. The profiles showed that among the 100 genes most significantly regulated by DcR3, 45 were upregulated and 55 were downregulated. The upregulated genes were associated with protein complex assembly, cell motility, regulation of transcription, cellular protein catabolic processes, cell membrane, nucleotide binding and glycosylation. The downregulated genes were associated with transcription regulator activity, RNA biosynthetic processes, cytoskeleton, zinc finger region, protein complex assembly, phosphate metabolic processes, mitochondrion, ion transport, nucleotide binding and cell fractionation. Further study of the genes detected in the current study may provide insight into the pathogenesis and treatment of rheumatoid arthritis by DcR3-TL1A signaling.