Work

HMGB1 facilitates PDGF-B production and angiogenesis in rheumatoid arthritis through RAF, MEK and ERK signaling

Year: 2025

Type: article

Abstract: Chronic systemic inflammation and autoimmunity are hallmarks of rheumatoid arthritis (RA), an inflammatory illness that gradually deteriorates the joints and results in permanent disability. An important pathogenic mechanism in RA is angiogenesis, which draws inflammatory leukocytes into the synovium and encourages the synthesis of damaging proteases and proinflammatory cytokines. High-mobility group box-1 (HMGB1) is a common nuclear protein with extracellular inflammatory ability that plays a crucial function in inflammatory disorders. Using data from the GEO dataset, the present report determined that the expression levels of HMGB1, the vascular marker CD34, and the angiogenic factor PDGF-B were remarkably higher in RA patients than in normal controls. HMGB1 treatment enhanced PDGF-B production in RA synovial fibroblasts (RASFs), while a PDGF-B antibody blocked HMGB1-treated RASFs-induced angiogenesis in HUVECs. We also revealed that the RAF, MEK, and ERK signaling pathways mediate HMGB1-induced PDGF-B production and angiogenesis. Thus, the HMGB1/PDGF-B axis may serve as a novel target for RA treatment.

Source: International Immunopharmacology

DOI: 10.1016/j.intimp.2025.115227