长非编码RNA H19调解STAT3依赖的质细胞和纤维细胞在全身性硬化症皮肤中的激活
Begoña Caballero-Ruiz1, Christopher W Wasson1, Rebecca L Ross1,2
1Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom.
Arthritis & rheumatology (Hoboken, N.J.)
|February 23, 2026
概括
长非编码RNA H19驱动纤维细胞激活和状细胞交叉在系统性硬化症 (SSc). 向H19可能为组织纤维化提供一种新的治疗策略.
科学领域:
- 皮肤病学 皮肤病学
- 分子生物学分子生物学
- 纤维化研究 纤维化研究
背景情况:
- 系统性硬化症 (SSc) 涉及纤维细胞和角质细胞的激活.
- 长非编码RNA H19在SSc纤维细胞及其外体中被上调.
- 在SSc病变发生过程中H19的作用仍然未被探索.
研究的目的:
- 调查H19在皮肤纤维细胞的profibrotic激活中的作用.
- 确定H19在SSc.中的纤维细胞 - 角质细胞交叉的参与.
- 探索H19作为SSc.的潜在治疗点.
主要方法:
- 从SSc患者和健康对照 (HC) 进行皮肤活检的分析.
- 在H19,STAT3和原1表达的现场杂交和免疫组织化学.
- 使用逆转录病毒转导和siRNA调节H19和STAT3的表达.
- 功能测定包括凝收缩和跨井共同培养.
主要成果:
- 在SSc皮肤和纤维细胞中增加的H19表达与profibrotic标志物相关联.
- H19 knockdown 降低了亲纤维细胞基因表达和纤维细胞收缩.
- 在HC纤维细胞中,H19的过度表达诱导了一种profibrotic表型.
- TGF-β,IL-6和IL-11通过STAT3激活增加了H19的表达.
- 在与SSc纤维细胞共培养的角质细胞中,H19敲击抑制了STAT3/STAT1激活.
结论:
- 长非编码RNA H19 是SSc病变发生的关键媒介.
- H19驱动着STAT3诱导的纤维细胞和角质细胞的纤维激活.
- H19代表了SSc.中的组织纤维化的一个有前途的治疗标.
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