Figure 2.

Diagram about the role of ferroptosis in RA. DMT1, divalent metal transporter 1; F2-I, isoprostane; FLS, fibroblast-like synoviocyte; FTH1, ferritin heavy chain 1; FTL, ferritin light chain; GSH, glutathione; GPX4, glutathione peroxidase 4; HSPA5, heat shock protein family A member 5; 4-HNE, 4-hydroxynonenal; IFN-γ, interferon-γ; IL-1β, interleukin-1β; IL-6, interleukin-6; MDA; malonaldehyde; NCOA4, nuclear receptor coactivator 4; Nrf2, nuclear factor erythroid 2-related factor 2; RBC, red blood cell; sTfR, soluble transferrin receptor; TGF-β, transforming growth factor-β; TNF, tumor necrosis factor; TNFR, tumor necrosis factor receptor. Lipid peroxidation were observed in the blood, synovial tissue and synovial fluid of RA patients, as well as iron deposition in the synovium. There was evidence of ferroptosis in RA-FLSs and macrophages, but it has not been determined whether ferroptosis is hyperactive or inhibited. TNF could reduce the ferroptosis sensitivity of FLSs through TNFR, while other cytokines, including IL-1, IL-6, TGF-β and IFN-γ, could promote ferroptosis in FLSs.