Renin Cell Baroreceptor, a Nuclear Mechanotransducer Central for Homeostasis.
Renin Cell Baroreceptor, a Nuclear Mechanotransducer Central for Homeostasis.
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DOI：
10.1161/circresaha.120.318711
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发表时间：
2021-07-09
影响因子：
20.1
通讯作者：
Sequeira-Lopez MLS
中科院分区：
文献类型：
--
作者：
Watanabe H;Belyea BC;Paxton RL;Li M;Dzamba BJ;DeSimone DW;Gomez RA;Sequeira-Lopez MLS
表达肾素的细胞是对生存至关重要的肌内分泌细胞。它们被认为具有压力感应机制，压力感受器，可以检测血压的轻微变化，并以精确和同步的量合成和释放到循环中的肾素来维持血压和液体电解质平衡。这个令人困惑的压力感应结构的位置和性质自60多年前首次提出以来一直不为人知。目的：阐明肾素细胞压力感受器的定位和结构。我们使用了各种转基因小鼠，其中肾素细胞在体内暴露于低或高动脉压。此外，我们应用直接的机械刺激，即，气动压力或拉伸，直接作用于在不同条件和基质下培养的肾素细胞。灌注压和/或直接机械刺激的变化引起显着的变化，在肾素基因表达和肾素细胞的表型。重要的是，实验表明压力感受机制（压力感受器）存在于肾素细胞中;它需要在肾素细胞膜上通过整合素β1进行初始细胞外感受，并通过核纤层蛋白A/C转导至核膜和染色质。这些研究表明，神秘的压力感受器是一种核机械传感器，存在于肾素细胞本身，并负责通过核纤层蛋白A/C直接将细胞外物理力感测和传递到肾素细胞的染色质，以调节肾素基因表达，肾素生物利用度和稳态。
Renin-expressing cells are myoendocrine cells crucial for survival. They have been postulated to possess a pressure-sensing mechanism, a baroreceptor, that can detect slight changes in blood pressure and respond with precise and synchronized amounts of renin synthesized and released to the circulation to maintain blood pressure and fluid-electrolyte balance. The location and nature of this puzzling pressure-sensing structure have remained unknown since it was originally suggested over sixty years ago. To elucidate the location and structure of the renin cell baroreceptor. We used a variety of genetically modified mice whereby renin cells were exposed in vivo to either low or high arterial pressure. In addition, we applied direct mechanical stimuli, i.e., pneumatic pressure or stretch, directly to renin cells cultured under different conditions and substrata. Changes in perfusion pressure and/or direct mechanical stimuli induced significant changes in renin gene expression and the phenotype of renin cells. Importantly, the experiments show that the pressure-sensing mechanism (the baroreceptor) resides in the renin cells; it requires initial extracellular sensing by integrin β1 at the renin cell membrane and is transduced to the nuclear membrane and chromatin by lamin A/C. These studies show that the enigmatic baroreceptor is a nuclear mechanotransducer that resides in the renin cells per se and is responsible for the sensing and transmission of extracellular physical forces directly to the chromatin of renin cells via lamin A/C to regulate renin gene expression, renin bioavailability, and homeostasis.
影响因子：
19.6
作者：
Gomez, R. Ariel;Lopez, Maria Luisa S. Sequeira
通讯作者：
Lopez, Maria Luisa S. Sequeira