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Gene expression profiles in the rat streptococcal cell wall-induced arthritis model identified using microarray analysis.

Rioja I, Clayton CL, Graham SJ, Life PF, Dickson MC - Arthritis Res. Ther. (2004)

Bottom Line: The genes exhibiting the highest fold increase in expression on days -13.8, -13, or 3 were involved in chemotaxis, inflammatory response, cell adhesion and extracellular matrix remodelling.The majority of the downregulated genes were associated with metabolism, transport and regulation of muscle development.These findings improve our understanding of the molecular events that underlie the pathology in this animal model, which is potentially a valuable comparator to human rheumatoid arthritis (RA).

View Article: PubMed Central - HTML - PubMed

Affiliation: Rheumatoid Arthritis Disease Biology Department, GlaxoSmithKline, Medicines Research Centre, Stevenage, UK. inma_rioja@yahoo.com

ABSTRACT
Experimental arthritis models are considered valuable tools for delineating mechanisms of inflammation and autoimmune phenomena. Use of microarray-based methods represents a new and challenging approach that allows molecular dissection of complex autoimmune diseases such as arthritis. In order to characterize the temporal gene expression profile in joints from the reactivation model of streptococcal cell wall (SCW)-induced arthritis in Lewis (LEW/N) rats, total RNA was extracted from ankle joints from naive, SCW injected, or phosphate buffered saline injected animals (time course study) and gene expression was analyzed using Affymetrix oligonucleotide microarray technology (RAE230A). After normalization and statistical analysis of data, 631 differentially expressed genes were sorted into clusters based on their levels and kinetics of expression using Spotfire profile search and K-mean cluster analysis. Microarray-based data for a subset of genes were validated using real-time PCR TaqMan analysis. Analysis of the microarray data identified 631 genes (441 upregulated and 190 downregulated) that were differentially expressed (Delta > 1.8, P < 0.01), showing specific levels and patterns of gene expression. The genes exhibiting the highest fold increase in expression on days -13.8, -13, or 3 were involved in chemotaxis, inflammatory response, cell adhesion and extracellular matrix remodelling. Transcriptome analysis identified 10 upregulated genes (Delta > 5), which have not previously been associated with arthritis pathology and are located in genomic regions associated with autoimmune disease. The majority of the downregulated genes were associated with metabolism, transport and regulation of muscle development. In conclusion, the present study describes the temporal expression of multiple disease-associated genes with potential pathophysiological roles in the reactivation model of SCW-induced arthritis in Lewis (LEW/N) rat. These findings improve our understanding of the molecular events that underlie the pathology in this animal model, which is potentially a valuable comparator to human rheumatoid arthritis (RA).

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Representative graph of genes that were upregulated (Delta > 1.8 and P < 0.01) in arthritic joints from streptococcal cell wall (SCW)-induced arthritis model on day -13.8 (4 hours after systemic challenge), day -13 and day 3. The graphs represent the fold increase in gene expression (Delta) and the name of the genes associated with the following ontologies: apoptosis (A; red bars), regulation of cell cycle and cell proliferation (B; blue bars), transport (C; green bars) and regulation of transcription, DNA-dependent (D; yellow bars).
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Figure 2: Representative graph of genes that were upregulated (Delta > 1.8 and P < 0.01) in arthritic joints from streptococcal cell wall (SCW)-induced arthritis model on day -13.8 (4 hours after systemic challenge), day -13 and day 3. The graphs represent the fold increase in gene expression (Delta) and the name of the genes associated with the following ontologies: apoptosis (A; red bars), regulation of cell cycle and cell proliferation (B; blue bars), transport (C; green bars) and regulation of transcription, DNA-dependent (D; yellow bars).

Mentions: Analysis of RAE230A GeneChip® microarray data identified about 9000 probes (5479 upregulated and 3898 downregulated) that were differentially expressed to a highly significant degree (P < 0.01) in arthritic rat joints from the time course study. After applying selection criteria (Delta > 1.8 and P < 0.01), 631 of the dysregulated probes had well characterized full-length sequences in databases (441 upregulated and 190 downregulated) and 697 were unknown (ESTs; 444 upregulated and 253 downregulated). These genes are too numerous to describe in detail, and therefore we present a selected list of upregulated genes in Table 2 and Fig. 2, and a selection of downregulated genes based on the ontologies that reflect the major changes occurring in arthritic animals (Fig. 3). ESTs were excluded from Table 2 and from subsequent clustering analysis. See Additional file 1, which contains all genes that were upregulated and downregulated.


Gene expression profiles in the rat streptococcal cell wall-induced arthritis model identified using microarray analysis.

Rioja I, Clayton CL, Graham SJ, Life PF, Dickson MC - Arthritis Res. Ther. (2004)

Representative graph of genes that were upregulated (Delta > 1.8 and P < 0.01) in arthritic joints from streptococcal cell wall (SCW)-induced arthritis model on day -13.8 (4 hours after systemic challenge), day -13 and day 3. The graphs represent the fold increase in gene expression (Delta) and the name of the genes associated with the following ontologies: apoptosis (A; red bars), regulation of cell cycle and cell proliferation (B; blue bars), transport (C; green bars) and regulation of transcription, DNA-dependent (D; yellow bars).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1064886&req=5

Figure 2: Representative graph of genes that were upregulated (Delta > 1.8 and P < 0.01) in arthritic joints from streptococcal cell wall (SCW)-induced arthritis model on day -13.8 (4 hours after systemic challenge), day -13 and day 3. The graphs represent the fold increase in gene expression (Delta) and the name of the genes associated with the following ontologies: apoptosis (A; red bars), regulation of cell cycle and cell proliferation (B; blue bars), transport (C; green bars) and regulation of transcription, DNA-dependent (D; yellow bars).
Mentions: Analysis of RAE230A GeneChip® microarray data identified about 9000 probes (5479 upregulated and 3898 downregulated) that were differentially expressed to a highly significant degree (P < 0.01) in arthritic rat joints from the time course study. After applying selection criteria (Delta > 1.8 and P < 0.01), 631 of the dysregulated probes had well characterized full-length sequences in databases (441 upregulated and 190 downregulated) and 697 were unknown (ESTs; 444 upregulated and 253 downregulated). These genes are too numerous to describe in detail, and therefore we present a selected list of upregulated genes in Table 2 and Fig. 2, and a selection of downregulated genes based on the ontologies that reflect the major changes occurring in arthritic animals (Fig. 3). ESTs were excluded from Table 2 and from subsequent clustering analysis. See Additional file 1, which contains all genes that were upregulated and downregulated.

Bottom Line: The genes exhibiting the highest fold increase in expression on days -13.8, -13, or 3 were involved in chemotaxis, inflammatory response, cell adhesion and extracellular matrix remodelling.The majority of the downregulated genes were associated with metabolism, transport and regulation of muscle development.These findings improve our understanding of the molecular events that underlie the pathology in this animal model, which is potentially a valuable comparator to human rheumatoid arthritis (RA).

View Article: PubMed Central - HTML - PubMed

Affiliation: Rheumatoid Arthritis Disease Biology Department, GlaxoSmithKline, Medicines Research Centre, Stevenage, UK. inma_rioja@yahoo.com

ABSTRACT
Experimental arthritis models are considered valuable tools for delineating mechanisms of inflammation and autoimmune phenomena. Use of microarray-based methods represents a new and challenging approach that allows molecular dissection of complex autoimmune diseases such as arthritis. In order to characterize the temporal gene expression profile in joints from the reactivation model of streptococcal cell wall (SCW)-induced arthritis in Lewis (LEW/N) rats, total RNA was extracted from ankle joints from naive, SCW injected, or phosphate buffered saline injected animals (time course study) and gene expression was analyzed using Affymetrix oligonucleotide microarray technology (RAE230A). After normalization and statistical analysis of data, 631 differentially expressed genes were sorted into clusters based on their levels and kinetics of expression using Spotfire profile search and K-mean cluster analysis. Microarray-based data for a subset of genes were validated using real-time PCR TaqMan analysis. Analysis of the microarray data identified 631 genes (441 upregulated and 190 downregulated) that were differentially expressed (Delta > 1.8, P < 0.01), showing specific levels and patterns of gene expression. The genes exhibiting the highest fold increase in expression on days -13.8, -13, or 3 were involved in chemotaxis, inflammatory response, cell adhesion and extracellular matrix remodelling. Transcriptome analysis identified 10 upregulated genes (Delta > 5), which have not previously been associated with arthritis pathology and are located in genomic regions associated with autoimmune disease. The majority of the downregulated genes were associated with metabolism, transport and regulation of muscle development. In conclusion, the present study describes the temporal expression of multiple disease-associated genes with potential pathophysiological roles in the reactivation model of SCW-induced arthritis in Lewis (LEW/N) rat. These findings improve our understanding of the molecular events that underlie the pathology in this animal model, which is potentially a valuable comparator to human rheumatoid arthritis (RA).

Show MeSH
Related in: MedlinePlus