期刊
NATURE
卷 515, 期 7526, 页码 279-U308出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature13701
关键词
-
资金
- Wellcome Trust
- Medical Research Council
- Leeds Teaching Hospitals Trust Charitable Foundation
- British Heart Foundation
- University of Leeds
- China Scholarship Council
- BBSRC PhD Studentship
- Cancer Research UK Clinical Fellowship
- BBSRC-AstraZeneca PhD Studentship
- British Heart Foundation Fellowship
- MRC [MR/L019051/1, G1002076] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [1360947] Funding Source: researchfish
- British Heart Foundation [RG/13/1/30042, FS/12/54/29671, FS/12/80/29821, FS/14/22/30734] Funding Source: researchfish
- Medical Research Council [MR/L019051/1, G1002076] Funding Source: researchfish
The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic(1-5). Studies of sensory neurons have suggested Piezo proteins as subunits of Ca2+-permeable non-selective cationic channels for detection of noxious mechanical impact(6-8). Here we show Piezol (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezol profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezol channels as sensors of blood flow was shown by Piezol dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezol to confer sensitivity to shear stress on otherwise resistant cells. Down-stream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezol channels function as pivotal integrators in vascular biology.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据