Fibronectin-1 is a dominant mechanism for rheumatoid arthritis via the mediation of synovial fibroblasts activity

Abstract

Rheumatoid arthritis (RA) has a high incidence and adverse effects on patients, thus posing a serious threat to people’s life and health. However, the underlying mechanisms regarding the development of RA are still elusive. Herein, we aimed to evaluate the RA-associated molecular mechanisms using the scRNA-seq technique. We used the GEO database to obtain scRNA-seq datasets for synovial fibroblasts (SFs) from RA cases, and the genes were then analyzed using principal component analysis (PCA) and T-Stochastic Neighbor Embedding (TSNE) analyses. Bioinformatics evaluations were carried out for asserting the highly enriched signaling pathways linked to the marker genes, and the key genes related to RA initiation were further identified. According to the obtained results, 3 cell types (0, 1, and 2) were identified by TSNE and some marker genes were statistically upregulated in cell type 1 than the other cell types. These marker genes predominantly contributed to extracellular matrix (ECM) architecture, collagen-harboring ECM, and ECM structural components, and identified as enriched with PI3K/AKT signaling cascade. Notably, fibronectin-1 (FN-1) has been identified as a critical gene that is strongly linked to the development of SFs and has enormous promise for regulating the onset of RA. Moreover, such an investigation offers novel perspectives within onset/progression of RA, suggesting that FN-1 may be a key therapeutic target for RA therapies.

Proteomic profiling of extracellular vesicles in synovial fluid and plasma from Oligoarticular Juvenile Idiopathic Arthritis patients reveals novel immunopathogenic biomarkers

“…FN1 and NRP1) and in synovial inflammation, fibrosis, hyperplasia, angiogenesis, and/or joint degradation (e.g. CD109, CRTAC1, and LUM) and proposed as putative development/progression biomarkers or potential therapeutic targets in RA and/or OA (77,(158)(159)(160)(161)(162). No data on these proteins have been previously reported in JIA.…”

Advanced methods and novel biomarkers in autoimmune diseases ‑ a review of the recent years progress in systemic lupus erythematosus

“…An article by Orange et al showed increased expansion of preinflammatory mesenchymal cells (113), while Micheroli et al identified four distinct SF clusters (114). Yang et al studied scRNAseq datasets for SFs revealing Fibronectin-1 as an important gene in relation to RA disease progression (115). A recent review discusses the development of residential memory T cells in synovial tissue in RA patients and indicate a role for these cells in the transition from acute to chronic inflammation (116).…”