RNA-seq analysis of synovial fibroblasts in human rheumatoid arthritis

Abstract

The aim of the present study was to identify differentially expressed genes (DEGs) between individuals with rheumatoid arthritis (RA) and healthy controls, in order to provide a theoretical foundation for RA diagnosis and targeted gene therapy. Illumina mRNA sequence data (RNA‑Seq) corresponding to RA and control samples were downloaded from the Sequence Read Archive (SRA) database. Gene Ontology (GO) enrichment analysis was performed with the GOstat tool in order to identify over‑represented biological functions among DEGs, and the related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified using the KEGG Automatic Annotation Server (KAAS). A total of 293 DEGs were identified, among which 16 DEGs have been previously shown to associate with RA, such as those encoding matrix metalloproteinase‑1 (MMP‑1), interleukin‑1 receptor type 1 (IL1R1), and chemokine (C-X3-C motif) ligand 1 (CX3CL1). GO functional annotation and enrichment analysis showed that the DEGs are enriched for 309 GO terms, mainly protein‑protein interactions, membrane formation and stability. KEGG pathway analysis demonstrated that these DEGs are involved in 131 pathways, including Wnt and calcium signaling, and cell adhesion molecule (CAM)-related pathways. In conclusion, the results provide both expansive and detailed insights into the molecular pathogenesis of RA, particularly with regards to the development of therapeutic targets, and may inspire further experimentation aiming to identify new strategies for RA treatment.

Meta-Analysis of Maternal and Fetal Transcriptomic Data Elucidates the Role of Adaptive and Innate Immunity in Preterm Birth

“…IL-1 receptor type I has been studied as one of the potential biomarkers to predict heart failure in hypertensive patients ( 52 ) and was proposed as a candidate molecular target for rheumatoid arthritis treatment ( 53 ). In the pregnancy space, IL-1R1 has been investigated in endometrial tissues and chorioamnionitis ( 54 , 55 ) and has been found to be increased in PTBs stimulated by RU486 in rats ( 56 ).…”

<p>Role of Chemokines and Chemokine Receptors in Rheumatoid Arthritis</p>

“…[96][97][98][99] Moreover, stimulation by CX 3 CL1 was found to trigger the proliferation of fibroblasts and atherosclerosis as well as leading to an increased MMPs and further inflammation in RA joints. [100][101][102][103][104] Multiple studies in RA have been carried out with antagonists and/or neutralizing antibodies against chemokines including CCR1, CCR5, CXCR4, CXCR7, CCL19, CXCL10, CXCL12, and CXCL13, where they revealed potential to be future targets. 105,106 However, further understanding of the role of these chemokines in RA is quite essential.…”

Comparative morphofunctional analysis of fibroblast-like synoviocytes in human rheumatoid arthritis and mouse collagen-induced arthritis

“…The low expression of the IL-1β receptor in CIA-FLSs could explain the lack of activation of downstream signaling pathways and the lack of an increase in MMP-3 and IL-6 production [40]. However, IL-6 production has been observed after IL-1β stimulation in CIA-FLSs [40], but the researchers did not analyze the activation of the signaling pathways that was reported in our work. Our results suggest that the low activation and nonactivation of signaling pathways (p-ERK, p-p38, p-JNK and NF-κB transcription factor) was consistent with the lack of production of MMP-3 and IL-6 [41].…”

“…Although IL-1β is present on the in amed synovium in CIA [38,39], few studies have demonstrated the expression of the IL-1β receptor (IL1r1) in CIA-FLSs [37]. The low expression of the IL-1β receptor in CIA-FLSs could explain the lack of activation of downstream signaling pathways and the lack of an increase in MMP-3 and IL-6 production [40]. However, IL-6 production has been observed after IL-1β stimulation in CIA-FLSs [40], but the researchers did not analyze the activation of the signaling pathways that was reported in our work.…”