Department of Chemical Engineering, Stanford University, Stanford, California, USA.
Department of Materials, ETH Zürich, Zürich, Switzerland.
FASEB J. 2023 Dec;37(12):e23240. doi: 10.1096/fj.201902205RRRR.
One-way valves within lymphatic vessels are required for the efficient drainage of lymphatic fluids. Fluid flow is proposed to be a key cue in regulating both the formation and maintenance of lymphatic valves. However, to our knowledge, no previous study has systematically examined the response of LECs to the complex combination of spatially and temporally varying fluid flows that occur at lymphatic valves in vivo. We built an in vitro microfluidic device that reproduces key aspects of the flow environment found at lymphatic valves. Using this device, we found that a combination of spatially and temporally varying wall shear stresses (WSSs) led to upregulated transcription of PROX1 and FOXC2. In addition, we observed that combined spatial and temporal variations in WSS-modulated Ca signaling and led to increased cellular levels of NFATc1. These observations suggest that the physical cues generated by the flow environment present within lymphatic valves may act to activate key regulatory pathways that contribute to valve maintenance.
淋巴管内的单向阀对于淋巴液的有效引流是必需的。据推测，流体流动是调节淋巴管瓣膜形成和维持的关键线索。然而，据我们所知，以前没有研究系统地研究过 LEC 对体内淋巴管瓣膜处发生的空间和时间变化的复杂组合流体流动的反应。我们构建了一种体外微流控装置，该装置再现了淋巴管瓣膜处发现的流动环境的关键方面。使用该装置，我们发现空间和时间变化的壁切应力（WSS）的组合导致 PROX1 和 FOXC2 的转录上调。此外，我们观察到 WSS 调节的 Ca 信号的时空变化导致 NFATc1 细胞水平增加。这些观察结果表明，存在于淋巴管瓣膜内的流动环境产生的物理线索可能作用于激活对瓣膜维持有贡献的关键调节途径。
