RNA-seq analysis of synovial fibroblasts brings new insights into rheumatoid arthritis

We 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.Since 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.Rheumatoid arthritis [RA] is a chronic, systemic autoimmune disorder associated with both genetic and environmental factors. RA affects 1% of the world’s population, develops most commonly in adults between 40 – 70 years old, and occurs more frequently in women than in men [1-4]. 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 the subsequent activation and proliferation of synovial fibroblasts (SFs) [3,4]. Rheumatoid arthritis synovial fibroblasts (RASFs) produce additional cytokines, chemokines and matrix-degrading enzymes which ultimately leads t