氨酸脱甲基酶1 具有脱甲基酶依赖且在系统性硬化症中肌纤维细胞激活中的非规范性功能
Christopher W Wasson1, Esther Perez Barreiro2, Francesco Del Galdo1,3
1Leeds Institute of Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UK.
Cells
|March 26, 2025
概括
系统性硬化症 (SSc) 纤维细胞激活涉及氨酸特异性去甲基酶1 (LSD1). 虽然其催化活性很小,但LSD1在驱动纤维化方面发挥着关键的非正规作用,独立于当前的抑制剂.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 皮肤病学 皮肤病学
背景情况:
- 系统性硬化症 (SSc) 是一种自身免疫性疾病,导致皮肤和器官纤维化.
- 激活的纤维细胞 (肌纤维细胞) 在SSc中驱动组织纤维化.
- 长非编码RNAHOTAIR是SSc纤维细胞激活的已知驱动因素.
研究的目的:
- 研究氨酸特异性脱甲酶1 (LSD1) 在SSc纤维细胞激活中的作用.
- 阐明LSD1在亲纤维细胞基因表达中的功能机制.
主要方法:
- 研究了健康受试者和SSc患者的皮肤纤维细胞.
- 利用转化生长因子-β和其他纤维化的刺激.
- 研究了LSD1沉默及其催化活性的影响.
主要成果:
- 通过纤维刺激激活急性纤维细胞的过程中需要LSD1活性.
- 在HOTAIR驱动的纤维化和SSc纤维细胞表型维持中,LSD1的催化活性起不大作用.
- 沉默LSD1极大地影响亲纤维基因表达,表明非正规的脚手架功能.
结论:
- 在SSc亲纤维基因表达中,LSD1具有重要的,非正规的支架作用.
- 目前的LSD1抑制剂没有抑制这种功能,这表明需要新的治疗点.
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