Vascular tubulogenesis is tightly linked with physiological and pathological events in the living body. Endothelial cells (ECs), which are constantly exposed to hemodynamic forces, play a key role in tubulogenesis. Hydrostatic pressure in particular has been shown to elicit biophysical and biochemical responses leading to EC-mediated tubulogenesis. However, the relationship between tubulogenesis and hydrostatic pressure remains to be elucidated. Here, we propose a specific mechanism through which hydrostatic pressure promotes tubulogenesis. We show that pressure exposure transiently activates the Ras/extracellular signal-regulated kinase (ERK) pathway in ECs, inducing endothelial tubulogenic responses. Water efflux through aquaporin 1 and activation of protein kinase C via specific G protein–coupled receptors are essential to the pressure-induced transient activation of the Ras/ERK pathway. Our approach could provide a basis for elucidating the mechanopathology of tubulogenesis-related diseases and the development of mechanotherapies for improving human health.

血管微管发生与生物体内的生理和病理事件紧密相关。内皮细胞（ECs）不断受到血液动力的作用，在肾小管生成中起关键作用。特别是静水压已显示出引起EC介导的肾小管生成的生物物理和生化反应。然而，肾小管生成和静水压力之间的关系仍有待阐明。在这里，我们提出了一种通过静水压力促进肾小管生成的特殊机制。我们显示压力暴露会在ECs中瞬时激活Ras /细胞外信号调节激酶（ERK）途径，诱导内皮微管反应。通过水通道蛋白1的水流出以及通过特定的G蛋白偶联受体激活的蛋白激酶C，对于压力诱导的Ras / ERK途径的瞬时激活至关重要。我们的方法可以为阐明与肾小管生成有关的疾病的机械病理学以及改善人类健康的机械疗法的发展提供基础。