Piezo1 channels are mechanosensors in human fetoplacental endothelial cells.
Piezo1 channels are mechanosensors in human fetoplacental endothelial cells.
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DOI：
10.1093/molehr/gay033
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发表时间：
2018-10-01
影响因子：
4
通讯作者：
Beech DJ
中科院分区：
文献类型：
--
作者：
Morley LC;Shi J;Gaunt HJ;Hyman AJ;Webster PJ;Williams C;Forbes K;Walker JJ;Simpson NAB;Beech DJ
剪切应力敏感离子通道亚基Piezo1在人胎儿胎盘内皮细胞中是否具有重要的机械转导作用？Piezo1存在于人胎儿胎盘内皮细胞中并具有功能活性，Piezo1的破坏阻止了对剪切应力的正常反应。剪切力是胎盘血管系统成熟和功能的重要刺激因素，但检测和转导剪切力的分子机制尚不清楚。Piezo1通道是Ca2+可渗透的非选择性阳离子通道，其对于剪切应力传感和鼠胚胎脉管系统的成熟至关重要。我们通过研究来自健康妊娠的人胎儿胎盘内皮细胞（FpECs）来研究Piezo1与胎盘血管系统的相关性。从胎盘子叶分离内皮细胞并进行培养，用于管形成和细胞排列对剪切力的研究。此外，人胎盘动脉内皮细胞的分离和研究，立即膜片钳电生理。合成的Piezo1通道激动剂Yoda1引起细胞内Ca2+浓度的强烈升高，在约5.4 μM时发生50%的效应。通过RNA干扰敲低Piezo1抑制Yoda1反应，这与Piezo1通道介导的反应一致。Piezo1敲低也抑制了细胞向剪切应力方向的排列，而不损失细胞活力。从新鲜分离的内皮细胞膜片钳记录显示剪切应力激活的单通道，这是Piezo1的特征。胎儿胎盘内皮细胞分离和随后培养的体外性质可能影响FpEC特征和PIEZO 1表达。除了Piezo1之外，在其他系统中也提出了替代的剪切应力传感机制，并且也可能在胎盘中起作用。这些数据表明，Piezo1是胎盘血流敏感性的重要分子决定因素。建立和操纵调节剪切应力传感的分子机制可能会导致新的治疗策略，以改善胎盘的血流。不适用因LCM由医学研究理事会的临床研究培训奖学金和皇家妇产科医师学院资助，并得到了威康信托机构战略支持基金的支持。JS得到了威康信托和BHF中级研究奖学金的支持。HJG，CW，AJH和PJW分别得到了BHF，BBSRC和利兹教学医院慈善基金会的博士生奖学金的支持。所有作者均声明无利益冲突。
Does the shear stress sensing ion channel subunit Piezo1 have an important mechanotransduction role in human fetoplacental endothelium? Piezo1 is present and functionally active in human fetoplacental endothelial cells, and disruption of Piezo1 prevents the normal response to shear stress. Shear stress is an important stimulus for maturation and function of placental vasculature but the molecular mechanisms by which the force is detected and transduced are unclear. Piezo1 channels are Ca2+-permeable non-selective cationic channels which are critical for shear stress sensing and maturation of murine embryonic vasculature. We investigated the relevance of Piezo1 to placental vasculature by studying human fetoplacental endothelial cells (FpECs) from healthy pregnancies. Endothelial cells were isolated from placental cotyledons and cultured, for the study of tube formation and cell alignment to shear stress. In addition, human placental arterial endothelial cells were isolated and studied immediately by patch-clamp electrophysiology. The synthetic Piezo1 channel agonist Yoda1 caused strong elevation of the intracellular Ca2+ concentration with a 50% effect occurring at about 5.4 μM. Knockdown of Piezo1 by RNA interference suppressed the Yoda1 response, consistent with it being mediated by Piezo1 channels. Alignment of cells to the direction of shear stress was also suppressed by Piezo1 knockdown without loss of cell viability. Patch-clamp recordings from freshly isolated endothelium showed shear stress-activated single channels which were characteristic of Piezo1. The in vitro nature of fetoplacental endothelial cell isolation and subsequent culture may affect FpEC characteristics and PIEZO1 expression. In addition to Piezo1, alternative shear stress sensing mechanisms have been suggested in other systems and might also contribute in the placenta. These data suggest that Piezo1 is an important molecular determinant of blood flow sensitivity in the placenta. Establishing and manipulating the molecular mechanisms regulating shear stress sensing could lead to novel therapeutic strategies to improve blood flow in the placenta. Not applicable. LCM was funded by a Clinical Research Training Fellowship from the Medical Research Council and by the Royal College of Obstetricians and Gynaecologists, and has received support from a Wellcome Trust Institutional Strategic Support Fund. JS was supported by the Wellcome Trust and a BHF Intermediate Research Fellowship. HJG, CW, AJH and PJW were supported by PhD Studentships from BHF, BBSRC and the Leeds Teaching Hospitals Charitable Foundation respectively. All authors declare no conflict of interest.
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影响因子：
16.6
作者：
Cox CD;Bae C;Ziegler L;Hartley S;Nikolova-Krstevski V;Rohde PR;Ng CA;Sachs F;Gottlieb PA;Martinac B
通讯作者：
Martinac B
影响因子：
6.6
作者：
Lang, I;Pabst, MA;Desoye, G
通讯作者：
Desoye, G
影响因子：
6.1
作者：
Myatt, L;Eis, ALW;Lyall, F
通讯作者：
Lyall, F
影响因子：
16.6
作者：
Fotiou E;Martin-Almedina S;Simpson MA;Lin S;Gordon K;Brice G;Atton G;Jeffery I;Rees DC;Mignot C;Vogt J;Homfray T;Snyder MP;Rockson SG;Jeffery S;Mortimer PS;Mansour S;Ostergaard P
通讯作者：
Ostergaard P
影响因子：
4.3
作者：
Dardik, A;Chen, LL;Sumpio, BE
通讯作者：
Sumpio, BE