Systems biology of lymphatic transport

 描述（由申请人提供）：淋巴管可以通过压力驱动流动或主动泵送输送液体，必要时甚至可以克服重力。在正常生理学中，淋巴系统能够使用这些机制来有效地和动态地维持组织液稳态。然而，在某些疾病中，淋巴功能效率低下，导致组织水肿和免疫反应减弱。由于控制淋巴功能的机制还不清楚，我们目前没有有效的治疗方法可以恢复这些患者的淋巴功能。我们建议，淋巴液的运输是由互补的机械生物学机制，涉及Ca2+通量和一氧化氮。我们将通过开发淋巴转运和组织流体动力学的计算模型来测试这一假设。然后，我们将在淋巴功能的小鼠模型中验证模拟，并使用它来识别和测试水肿和淋巴流受损的新疗法。

 DESCRIPTION (provided by applicant): Lymphatic vessels can transport fluid either by pressure-driven flow or by active pumping, even against gravity when necessary. In normal physiology, the lymphatic system is able to use these mechanisms to effectively and dynamically maintain tissue fluid homeostasis. In some diseases, however, lymphatic function is inefficient, resulting in tissue edema and weakened immune response. Because the mechanisms that control lymphatic function are not well-understood, we currently have no effective therapies that can restore lymphatic function in these patients. We propose that transport of lymph is controlled by complementary mechanobiological mechanisms involving Ca2+ fluxes and nitric oxide. We will test this hypothesis by developing a computational model of lymphatic transport and tissue fluid dynamics. We will then validate the simulations in a mouse model of lymphatic function and use it to identify and test novel treatments for edema and impaired lymph flow.