周血管细胞作为血管毛细管中机械和结构变化的关键媒介
Cristiane M Franca1,2,3, Maria Elisa Lima Verde1,2,3, Alice Correa Silva-Sousa1,2,3
1Knight Cancer Precision Biofabrication Hub, Knight Cancer Institute, OHSU, Portland, OR 97201, USA.
Science advances
|January 10, 2025
概括
周血管细胞调解毛细血管对疾病中的纤维化细胞外基质 (ECM) 变化的反应. 这些细胞中的NOTCH3信号驱动血管泄漏和炎症,揭示了纤维性疾病的新机制.
科学领域:
- 生物医学工程 生物医学工程
- 血管生物学 血管生物学
- 细胞外矩阵研究 细胞外矩阵研究
背景情况:
- 慢性和炎症性疾病的特征是纤维化,硬的细胞外基质 (ECM) 和异常的微血管毛细血管.
- 将ECM变化与微血管反应联系在一起的机制在很大程度上是未知的.
- 周血管细胞对于血管完整性和功能至关重要.
研究的目的:
- 研究周血管细胞在调解血管毛细血管对改变的ECM反应中的作用.
- 阐明在纤维状况下参与内皮-周血管细胞通信的信号通路.
- 了解NOTCH3信号在血管适应ECM变化的贡献.
主要方法:
- 使用微生理学"芯片上的毛细血管"模型.
- 在健康的或纤维化的原基质结构中设计的毛细血管.
- 评估了周血管细胞迁移,周细胞分化,血管泄漏和基因表达.
- 研究了NOTCH3信号传导的作用,通过沉默其在周围血管细胞中的表达.
主要成果:
- 纤维化ECM中的毛细血管表现出异常的周围血管细胞迁移和减少的周围细胞分化.
- 在纤维状况下观察到血管泄漏增加和炎症/重塑基因的上调.
- 鉴定出NOTCH3信号传递是这些反应的关键调节者,它调解了内皮-周血管细胞通信.
- 单独的内皮细胞或带有沉默NOTCH3的周血管细胞对ECM变化的反应很小.
结论:
- 周血管细胞通过NOTCH3信号传递,是血管毛细血管对ECM纤维化反应的关键调解者.
- 这项研究揭示了纤维化疾病中血管功能障碍的新机制.
- 研究结果强调NOTCH3是治疗慢性炎症疾病中血管并发症的潜在治疗点.
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