Piezol integration of vascular architecture with physiological force

被引：880

作者：

Li, Jing ^{[1
,2
]}

Hou, Bing ^{[1
,2
]}

Tumova, Sarka ^{[1
,2
]}

Muraki, Katsuhiko ^{[3
]}

Bruns, Alexander ^{[1
,2
]}

Ludlow, Melanie J. ^{[1
,2
]}

Sedo, Alicia ^{[1
,2
]}

Hyman, Adam J. ^{[1
,2
]}

McKeown, Lynn ^{[1
,2
]}

Young, Richard S. ^{[1
,2
]}

Yuldasheva, Nadira Y. ^{[1
,2
]}

Majeed, Yasser ^{[1
,2
]}

Wilson, Lesley A. ^{[1
,2
]}

Rode, Baptiste ^{[1
,2
]}

Bailey, Marc A. ^{[1
,2
]}

Kim, Hyejeong R. ^{[5
]}

Fu, Zhaojun ^{[1
,2
]}

Carter, Deborah A. L. ^{[1
,2
]}

Bilton, Jan ^{[1
,2
]}

Imrie, Helen ^{[1
,2
]}

Ajuh, Paul ^{[6
]}

Dear, T. Neil ^{[1
,2
]}

Cubbon, Richard M. ^{[1
,2
]}

Kearney, Mark T. ^{[1
,2
]}

Prasad, K. Raj ^{[4
]}

Evans, Paul C. ^{[5
]}

Ainscough, Justin F. X. ^{[1
,2
]}

Beech, David J. ^{[1
,2
]}

机构：

[1] Univ Leeds, Sch Med, Leeds LS2 9JT, W Yorkshire, England

[2] Univ Leeds, Multidisciplinary Cardiovasc Res Ctr, Leeds LS2 9JT, W Yorkshire, England

[3] Aichi Gakuin Univ, Sch Pharm, Chikusa Ku, Nagoya, Aichi 4648650, Japan

[4] St James Univ Hosp, Dept Hepatobiliary & Transplant Surg, Leeds LS9 7TF, W Yorkshire, England

[5] Univ Sheffield, Sheffield S10 2RX, S Yorkshire, England

[6] Dundee Cell Prod Ltd, Dundee DD1 5JJ, Scotland

来源：

NATURE | 2014年 / 515卷 / 7526期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金; 英国医学研究理事会;

关键词：

ACTIVATED CATION CHANNELS; FLUID SHEAR-STRESS; ENDOTHELIAL-CELLS; PROTEOME ANALYSIS; DISTURBED FLOW; CALPAIN; MECHANOTRANSDUCTION; TISSUES; GENE; MICE;

D O I：

10.1038/nature13701

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：279 / U308

页数：15

共 37 条

[1] Ciliary Polycystin-2 Is a Mechanosensitive Calcium Channel Involved in Nitric Oxide Signaling Cascades [J].