scholarly journals DDR2–CYR61–MMP1 Signaling Pathway Promotes Bone Erosion in Rheumatoid Arthritis Through Regulating Migration and Invasion of Fibroblast‐Like Synoviocytes

2019 ◽  
pp. e3688 ◽  
Author(s):  
Tong‐Lie Huang ◽  
Nan Mu ◽  
Jin‐Tao Gu ◽  
Zhen Shu ◽  
Kuo Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Signaling Pathway ◽  
Bone Erosion ◽  
Migration And Invasion ◽  
Fibroblast Like Synoviocytes

IRF9 Affects the TNF-Induced Phenotype of Rheumatoid-Arthritis Fibroblast-Like Synoviocytes via Regulation of the SIRT-1/NF-κB Signaling Pathway

2020 ◽  
Vol 209 (2–3) ◽  
pp. 110-119
Author(s):  
Fan Jiang ◽  
Hong-Yi Zhou ◽  
Li-Fang Zhou ◽  
Wei Zeng ◽  
Li-Han Zhao
Keyword(s):  
Rheumatoid Arthritis ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Biological Features ◽  
Induced Changes ◽  
Signaling Activity ◽  
Fibroblast Like Synoviocytes

<b><i>Objective:</i></b> To discuss how IRF9 affects the fibroblast-like synoviocytes (FLS) in TNF-induced rheumatoid arthritis (RA) via the SIRT-1/NF-κB signaling pathway. <b><i>Methods:</i></b> RA-FLS were isolated and divided into control, sh-IRF9, TNF, TNF + sh-Ctrl, TNF + sh-IRF9, TNF + sh-SIRT1, and TNF + sh-IRF9 + sh-SIRT1 groups. Biological features of FLS were evaluated by MTT, wound healing, and Transwell assays, respectively. Cell apoptosis and cycle were assessed flow cytometrically. Inflammatory cytokines were determined through enzyme-linked immunosorbent assay (ELISA), while IRF9 expression and SIRT1/NF-κB signaling pathway activity were measured by Western blotting. <b><i>Results:</i></b> TNF increased IRF9 expression as well as NF-κB signaling activity and down-regulated SIRT1 of RA-FLS. Silencing IRF9 resulted in up-regulation of SIRT1 and blocked NF-κB signaling, with significant decreases in TNF-induced cell viability, migration, and invasion, prominent enhancement in apoptosis and the proportion of cells in G0/G1 phase, but a decrease in the proportion of cells in S and G2/M phases, and reduced levels of inflammatory cytokines. However, these changes were totally abolished after silencing SIRT1, i.e., the IRF9 shRNA-induced inhibitory effect on the growth of RA-FLS was reversed. <b><i>Conclusion:</i></b> Silencing IRF9 curbs the activity of the NF-κB signaling pathway via up-regulating SIRT-1, to further suppress TNF-induced changes in the malignant features of RA-FLS, and the secretion of inflammatory cytokines, with the promoted apoptosis.

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