Abstract
BackgroundRheumatoid arthritis (RA) is a chronic autoimmune-disease of unknown origin that primarily affects the joints and ultimately leads to their destruction. Growing evidence suggests that synvovial fibroblasts play important roles in the initiation and the perpetuation of RA but underlying molecular mechanisms are not understood fully. In the present study, Illumina RNA sequencing was used to profile two human normal control and two rheumatoid arthritis synvovial fibroblasts (RASFs) transcriptomes to gain insights into the roles of synvovial fibroblasts in RA.ResultsWe found that besides known inflammatory and immune responses, other novel dysregulated networks and pathways such as Cell Morphology, Cell-To-Cell Signaling and Interaction, Cellular Movement, Cellular Growth and Proliferation, and Cellular Development, may all contribute to the pathogenesis of RA. Our study identified several new genes and isoforms not previously associated with rheumatoid arthritis. 122 genes were up-regulated and 155 genes were down-regulated by at least two-fold in RASFs compared to controls. Of note, 343 known isoforms and 561 novel isoforms were up-regulated and 262 known isoforms and 520 novel isoforms were down-regulated by at least two-fold. The magnitude of difference and the number of differentially expressed known and novel gene isoforms were not detected previously by DNA microarray.ConclusionsSince the activation and proliferation of RASFs has been implicated in the pathogenesis of rheumatoid arthritis, further in-depth follow-up analysis of the transcriptional regulation reported in this study may shed light on molecular pathogenic mechanisms underlying synovial fibroblasts in arthritis and provide new leads of potential therapeutic targets.
Highlights
Rheumatoid arthritis (RA) is a chronic autoimmune-disease of unknown origin that primarily affects the joints and leads to their destruction
RNA sequencing Human synovial fibroblasts (SFs) RNAs from two healthy control donors and two patients with RA were purchased from Cell Applications, Inc. (San Diego, CA)
Quality analysis of RNA sequencing (RNA-seq) data Real-time analysis of the sequencing run was performed by the Illumina HiSeq Control Software
Summary
Rheumatoid arthritis (RA) is a chronic autoimmune-disease of unknown origin that primarily affects the joints and leads to their destruction. XAlthough the etiology of the disease has not been elucidated fully, the pathogenesis of RA is characterized by the influx of cells from both the innate and the adaptive immune systems [5] These cells induce increased pro-inflammatory cytokine production, decreased synthesis of anti-inflammatory cytokines, and of new genes and pathways that can be targeted for therapeutic intervention. We found significant differences in the expression levels of both genes and gene isoforms between normal SFs and RASFs RNA samples These data provide broader and deeper insights, with respect to isoform expression, into the effect of RA on the transcriptional regulation of synovial fibroblasts and a rich resource for further experimentation into the pathogenesis of the disease
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