Mechanoinduction of lymph vessel expansion
Mechanoinduction of lymph vessel expansion
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DOI：
10.1038/emboj.2011.456
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发表时间：
2012-02-15
期刊：
影响因子：
11.4
通讯作者：
Lammert, Eckhard
中科院分区：
文献类型：
--
作者：
Planas-Paz, Lara;Strilic, Boris;Lammert, Eckhard
在哺乳动物胚胎中，几乎没有发现影响器官发育和功能的机械信号。在这里，我们报告了间质或细胞外液体体积的增加机械地诱导器官系统的生长，即淋巴管系统。我们首先证明了发育中的小鼠胚胎中淋巴管的扩张与间质压力和淋巴管内皮细胞(LEC)伸长的峰值相关。在“失液”实验中，我们发现抽吸间质液可以缩短晶状体上皮细胞的长度，减少血管内皮生长因子受体-3(VEGFR3)的酪氨酸磷酸化，并抑制LEC的增殖。相反，在“流体增益”实验中，增加间质液体的量会延长晶状体上皮细胞，并增加VEGFR3的磷酸化和LEC的增殖。最后，我们提供了遗传证据，表明β1整合素是晶状体上皮细胞对液体积聚和细胞拉伸的增殖反应所必需的，因此是淋巴管扩张和液体排出所必需的。因此，我们提出了一种新的与生理相关的VEGFR3激活模式，该模式基于机械转导，对于哺乳动物胚胎的正常发育和液体动态平衡是必不可少的。EMBO期刊(2012)31,788-804。DOI：10.1038/Intemj.2011.456；2011年12月13日在线发布
In the mammalian embryo, few mechanical signals have been identified to influence organ development and function. Here, we report that an increase in the volume of interstitial or extracellular fluid mechanically induces growth of an organ system, that is, the lymphatic vasculature. We first demonstrate that lymph vessel expansion in the developing mouse embryo correlates with a peak in interstitial fluid pressure and lymphatic endothelial cell (LEC) elongation. In 'loss-of-fluid' experiments, we then show that aspiration of interstitial fluid reduces the length of LECs, decreases tyrosine phosphorylation of vascular endothelial growth factor receptor-3 (VEGFR3), and inhibits LEC proliferation. Conversely, in 'gain-of-fluid' experiments, increasing the amount of interstitial fluid elongates the LECs, and increases both VEGFR3 phosphorylation and LEC proliferation. Finally, we provide genetic evidence that beta 1 integrins are required for the proliferative response of LECs to both fluid accumulation and cell stretching and, therefore, are necessary for lymphatic vessel expansion and fluid drainage. Thus, we propose a new and physiologically relevant mode of VEGFR3 activation, which is based on mechanotransduction and is essential for normal development and fluid homeostasis in a mammalian embryo. The EMBO Journal (2012) 31, 788-804. doi: 10.1038/emboj.2011.456; Published online 13 December 2011