Inhibition of LSD1 via SP2509 attenuated the progression of rheumatoid arthritis.

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC

ACS Applied Electronic Materials Pub Date : 2024-08-01 Epub Date: 2024-05-09 DOI:10.1007/s12026-024-09486-5

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

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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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通过 SP2509 抑制 LSD1 可减轻类风湿性关节炎的恶化。

类风湿性关节炎（RA）是一种慢性自身免疫性疾病，其特点是滑膜增生、脓肿形成以及软骨和骨破坏。赖氨酸特异性去甲基化酶 1（LSD1）是一种参与转录调控的酶，在类风湿性关节炎发病过程中，它在滑膜炎症、成纤维细胞样滑膜细胞迁移和侵袭中的作用尚不明确。在本研究中，我们观察到 LSD1 在 RA 滑膜组织和 TNF-α 刺激的 MH7A 细胞中表达增加。LSD1拮抗剂SP2509直接降低了LSD1的表达，并逆转了TNF-α诱导的炎症、凋亡、增殖和自噬相关蛋白水平的升高。此外，SP2509 还能抑制 MH7A 细胞的迁移能力，而 TNF-α 会增强迁移能力。在CIA模型中，SP2509治疗可改善RA的发展，减少促炎细胞因子的表达，减轻关节病理症状。这些发现强调了LSD1在RA中的重要性，并提出了SP2509的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Electronic Materials Multiple-

CiteScore

7.20

自引率

4.30%

发文量

567