Smad3的依赖cystathionine γ-lyase的S-硫化:一种新的目标来缓解系统性硬化症中的纤维化
Jiani Liu1,2, Yangfan Xiao3,4, Licong Liu1,2
1Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Arthritis & rheumatology (Hoboken, N.J.)
|February 9, 2026
概括
降低的cystathionine γ-lyase (CSE) /硫化 (H2S) 水平与系统性硬化症 (SSc) 有关. 恢复CSE/H2S通过修改Smad3来保护纤维化,为SSc.提供了潜在的治疗策略.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 囊氨酸γ-酶 (CSE) 和硫化 (H2S) 途径对于调节组织纤维化是至关重要的.
- 系统性硬化症 (SSc) 是一种纤维性疾病,具有复杂的潜在机制.
- 了解CSE/H2S轴在SSc中的作用对于开发有针对性的疗法至关重要.
研究的目的:
- 调查CSE/H2S轴在系统性硬化症 (SSc) 病变发生过程中的作用.
- 探索CSE/H2S通过哪些分子机制影响SSc.中的纤维化.
- 为了确定SSc治疗的CSE/H2S途径中的潜在治疗点.
主要方法:
- 在SSc患者和健康对照中评估了CSE/H2S水平.
- 使用人类皮肤纤维细胞和体内纤维化小鼠模型.
- 采用了CSE抑制/过度表达,H2S调制和S-硫化蛋白质组学.
- 进行了分子动力学模拟,并生成了Smad3突变体.
主要成果:
- SSc患者表现出降低的CSE/H2S水平和全球S-硫化.
- CSE抑制加剧了细胞外基质沉积,而CSE过度表达减轻了纤维化.
- CSE过度表达增强了Smad3的S-硫化,抑制了TGF-β1/Smad3的信号传递.
- Smad3 囊121被确定为一个关键的S-硫化位点,调解抗纤维效应.
结论:
- Smad3 S-硫化是SSc中CSE/H2S轴的抗纤维作用的关键机制.
- CSE/H2S-Smad3轴代表了系统性硬化症的一个有前途的治疗标.
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