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09-05-2024 | Rheumatoid Arthritis | Research

Inhibition of LSD1 via SP2509 attenuated the progression of rheumatoid arthritis

Authors: Ziliang Yu, Peipei Li, Dagong Gao, Yalong Hu, Fei Xia, Lei Liu, Jian Liu, Wei Liu, Haiping Zhang

Published in: Immunologic Research

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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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Metadata
Title
Inhibition of LSD1 via SP2509 attenuated the progression of rheumatoid arthritis
Authors
Ziliang Yu
Peipei Li
Dagong Gao
Yalong Hu
Fei Xia
Lei Liu
Jian Liu
Wei Liu
Haiping Zhang
Publication date
09-05-2024
Publisher
Springer US
Published in
Immunologic Research
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-024-09486-5