Mechanosensing in developing lymphatic vessels.
Mechanosensing in developing lymphatic vessels.
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DOI：
10.1007/978-3-7091-1646-3_3
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
L. Planas-Paz;E. Lammert
中科院分区：
文献类型：
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作者：
L. Planas-Paz;E. Lammert
淋巴管系统负责体液平衡、免疫细胞、炎症分子和膳食脂质的运输。它由淋巴毛细血管网络组成，这些毛细血管汇集成淋巴血管，最终将液体带回血液循环。淋巴内皮细胞（LECs）排列在淋巴毛细血管上，呈现松散重叠的细胞间连接和支持液体排泄的锚定细丝。当组织内的间质液积聚时，细胞外基质（ECM）膨胀并拉动锚定细丝。这导致LEC连接打开，并允许间质液摄取。吸收的液体随后在聚集的淋巴管中运输，这些淋巴管表现出腔内阀，防止淋巴液回流，平滑肌细胞依次收缩以推动淋巴液。机械转导涉及将机械刺激转化为生物反应。LECs可以感知并响应ECM刚度、流体压力诱导的细胞拉伸和流体流动诱导的剪切应力的变化。这些信号如何影响LEC功能和淋巴管生长可以通过不同的机械转导实验在体外和一定程度上在体内进行研究。在本章中，我们将集中讨论在胚胎发育和继发性淋巴水肿期间调节淋巴管扩张的机械力。在小鼠胚胎中，最近的研究表明，间质液的数量通过由β1整合素和血管内皮生长因子受体-3 （VEGFR3）形成的机械感觉复合物决定淋巴管扩张的程度。该模型也适用于继发性淋巴水肿。
The lymphatic vasculature is responsible for fluid homeostasis, transport of immune cells, inflammatory molecules, and dietary lipids. It is composed of a network of lymphatic capillaries that drain into collecting lymphatic vessels and ultimately bring fluid back to the blood circulation. Lymphatic endothelial cells (LECs) that line lymphatic capillaries present loose overlapping intercellular junctions and anchoring filaments that support fluid drainage. When interstitial fluid accumulates within tissues, the extracellular matrix (ECM) swells and pulls the anchoring filaments. This results in opening of the LEC junctions and permits interstitial fluid uptake. The absorbed fluid is then transported within collecting lymphatic vessels, which exhibit intraluminal valves that prevent lymph backflow and smooth muscle cells that sequentially contract to propel lymph.Mechanotransduction involves translation of mechanical stimuli into biological responses. LECs have been shown to sense and respond to changes in ECM stiffness, fluid pressure-induced cell stretch, and fluid flow-induced shear stress. How these signals influence LEC function and lymphatic vessel growth can be investigated by using different mechanotransduction assays in vitro and to some extent in vivo.In this chapter, we will focus on the mechanical forces that regulate lymphatic vessel expansion during embryonic development and possibly secondary lymphedema. In mouse embryos, it has been recently shown that the amount of interstitial fluid determines the extent of lymphatic vessel expansion via a mechanosensory complex formed by β1 integrin and vascular endothelial growth factor receptor-3 (VEGFR3). This model might as well apply to secondary lymphedema.