划分的转录标tmtc1维持了血管平衡
Na Yoon Paik1, Jacob Neethling1, Mumtaz Anwar1
1Department of Pharmacology and Regenerative Medicine, University of Illinois at Chicago College of Medicine, Chicago, IL, 60612, USA.
Cellular and molecular life sciences : CMLS
|August 27, 2024
概括
切口信号通过调节VE-cadherin处理来维持肺血管完整性. 阻断Notch信号增加了血管透性,导致急性肺损伤,突出了Notch信号.
科学领域:
- 肺和血管生物学
- 细胞和分子生物学是细胞和分子生物学.
- 信号通道的信号通道.
背景情况:
- 肺功能依赖于强大的内皮屏障,这对于预防急性肺损伤至关重要.
- 破坏内皮屏障完整性导致血管透性增加和肺.
- 诺奇信号在维持肺血管完整性的作用尚未完全理解.
研究的目的:
- 研究Notch信号转录标在维护肺血管完整性的作用.
- 确定Notch信号是否对于维持肺部内皮屏障至关重要.
- 为了识别参与血管平衡的新型Notch目标.
主要方法:
- 使用内皮特异性诺奇功能丧失的小鼠模型 (DNMAML和诺奇1淘汰).
- 在体内和隔离的初级肺内皮细胞中评估了血管透性.
- 在肺内皮细胞上进行RNA测序,以识别Notch转录标.
- 研究了已识别的Notch目标的相互作用和功能,特别是tmtc1,与VE-cadherin.
主要成果:
- 内皮特异性Notch抑制 (DNMAML和Notch1损失) 显著增加了肺血管的透性.
- 通过DNMAML的Pan-Notch抑制导致更严重的血管透性表型.
- RNA测序确定了跨膜O-mannosyltransferase向卡德林1 (tmtc1) 作为一个新的Notch目标.
- tmtc1直接与VE-cadherin相互作用,并调节其从内细胞网膜的运输.
结论:
- 切口信号转录维护内皮附着结和血管平衡.
- 诺奇-tmtc1-VE-cadherin轴对正确的VE-cadherin处理和内皮屏障功能至关重要.
- 准Notch信号通路可能为急性肺损伤提供治疗策略.
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