基底纤维素的增加足以促进多余的内皮细胞矩阵组合,导致局部屏障功能障碍
Henry A Resnikoff1, Jean E Schwarzbauer1
1Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
Molecular biology of the cell
|July 24, 2024
概括
血管中过多的纤维素 (FN) 基质积累会破坏内皮细胞功能,导致屏障功能障碍和疾病进展. 针对FN积累可能为纤维化提供治疗策略.
科学领域:
- 血管生物学 血管生物学
- 细胞外矩阵生物学 细胞外矩阵生物学
- 细胞生理学 细胞生理学
背景情况:
- 子内皮细胞外细胞矩阵 (ECM) 调节内皮细胞 (EC) 的行为.
- 纤维素 (FN),一个ECM蛋白质,在健康的血管中稀缺,但在疾病中增加,与内皮功能障碍相关.
研究的目的:
- 调查过度的纤维内素矩阵组合在破坏内皮细胞功能和屏障完整性方面的因果作用.
主要方法:
- 通过在Transwell插件的基底侧添加外源性FN来模拟增加的纤维素蛋白表达.
- 分析了剂量依赖的纤维素基因组合及其与EC形态,VE-cadherin结,细胞循环和屏障透性的相关性.
- 评估瘤细胞对内皮单层的粘附.
主要成果:
- 外源性FN剂量依赖性增加的子内皮质FN矩阵组合.
- 区域FN矩阵的增加与破坏的EC形态,VE-cadherin连接和细胞周期相关.
- 增加的FN矩阵先于内皮单层失调和泄漏,增强瘤细胞粘附.
结论:
- 脑内膜下纤维素基因基质的积累是导致脑内膜单层失调和泄漏的因素.
- 调节纤维内素积累呈现出控制纤维化和相关疾病的潜在治疗目标.
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