矩阵刚度调节了在全身性硬化症中纤维细胞纤维细胞分化和纤维细胞位激活
Ludwig Ueberall1, Hashem Mohammadian1, Richard Demmler1
1Department of Internal Medicine 3 -Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Annals of the rheumatic diseases
|June 27, 2025
概括
在系统性硬化 (SSc) 中,矩阵刚度通过促进原生纤维细胞分化为肌纤维细胞来驱动纤维化. 这一发现突出了生物力学线索作为SSc纤维化潜在的治疗点.
科学领域:
- 生物医学科学 生物医学科学
- 细胞生物学 细胞生物学
- 皮肤病学 皮肤病学
背景情况:
- 系统性硬化 (SSc) 中纤维化进展与矩阵度有关.
- 纤维细胞异质性和子集不平衡与纤维瘤疾病有关.
- 纤维化中的生物力学线索和纤维细胞动态之间的相互作用尚未研究.
研究的目的:
- 研究矩阵刚性如何影响纤维细胞转录状态.
- 确定矩阵刚度对纤维细胞系特征在纤维化皮肤中的影响.
主要方法:
- 使用3D原I培养系统来改变矩阵刚度.
- 进行RNA测序以识别性响应基因表达.
- 来自SSc和健康皮肤的综合单细胞和空间转录基因数据.
主要成果:
- 增加的矩阵刚度诱导出明显的纤维细胞转录特征,在SSc.中放大.
- 由矩阵刚性驱动的PI16+原生细胞分化为SFRP2+COMP+PU.1+肌纤维细胞.
- 焦点粘附激酶抑制破坏了这种机械传导驱动的血统过渡.
结论:
- 矩阵刚性促进纤维细胞前体分化为肌纤维细胞,维持纤维化.
- 这个过程独立于炎症触发因素而发生.
- 生物机械信号代表了SSc纤维化治疗的新治疗标.
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