AI Article Synopsis
- Rheumatoid arthritis (RA) is a long-lasting autoimmune disease that leads to inflammation and damage in joints, with key characteristics including inflammation of the synovial membrane and destruction of cartilage and bone.
- The study found that an enzyme called lysine-specific demethylase 1 (LSD1) is more active in RA tissues and plays a role in inflammation and cell movement related to RA.
- The drug SP2509, which blocks LSD1, showed promise in reducing inflammation and joint damage in RA models by lowering pro-inflammatory proteins and inhibiting the migration of cells involved in RA progression.
Article Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia, pannus formation, and cartilage and bone destruction. Lysine-specific demethylase 1 (LSD1), an enzyme involved in transcriptional regulation, has an unclear role in synovial inflammation, fibroblast-like synoviocytes migration, and invasion during RA pathogenesis. In this study, we observed increased LSD1 expression in RA synovial tissues and in TNF-α-stimulated MH7A cells. SP2509, an LSD1 antagonist, directly reduced LSD1 expression and reversed the elevated levels of proteins associated with inflammation, apoptosis, proliferation, and autophagy induced by TNF-α. Furthermore, SP2509 inhibited the migratory capacity of MH7A cells, which was enhanced by TNF-α. In CIA models, SP2509 treatment ameliorated RA development, reducing the expression of pro-inflammatory cytokines and alleviating joint pathological symptoms. These findings underscore the significance of LSD1 in RA and propose the therapeutic potential of SP2509.
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| http://dx.doi.org/10.1007/s12026-024-09486-5 | DOI Listing |
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