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

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.

Herbal adaptogens combined with protein fractions from bovine colostrum and hen egg yolk reduce liver TNF-α expression and protein carbonylation in Western diet feeding in rats

“…Differentially expressed liver mRNAs were considered to be significant when WD + AF/CTL fold-change values > ±1.5 and an independent t -test p-value < 0.01, whereas the same gene was not differentially expressed between WD/CTL (p > 0.05). Of note, these analyses thresholds are similar to other recent RNA-seq publications, which have used a 1.5-to-2.0 fold-change cut-off and similar p-value significant thresholds [35-37]. Genes that were found to be altered with AF supplementation were subsequently entered into Ingenuity Pathway Analysis (Qiagen) to elucidate gene networks and/or biological functions within the liver that were altered with AF supplementation.…”

Loss of Cdk5 function in the nucleus accumbens decreases wheel running and may mediate age‐related declines in voluntary physical activity

“…We implemented the following filters based on previous studies (Heruth et al . ; Song et al . ; Zhang et al .…”

Nucleus accumbens neuronal maturation differences in young rats bred for low versus high voluntary running behaviour

“…While a ±1.25‐fold cut‐off ( P < 0.01) threshold may seem statistically liberal compared to other publications using 1.5‐ to 2.0‐fold change cut‐offs to examine transcriptomic differences between treatments (Heruth et al . ; Song et al . ; Zhang et al .…”