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.
Keyphrases
- rheumatoid arthritis
- disease activity
- oxidative stress
- induced apoptosis
- cell cycle arrest
- poor prognosis
- endoplasmic reticulum stress
- ankylosing spondylitis
- cell death
- interstitial lung disease
- signaling pathway
- pi k akt
- gene expression
- multiple sclerosis
- extracellular matrix
- postmenopausal women
- bone mineral density
- idiopathic pulmonary fibrosis
- soft tissue