Systems biology of lymphatic transport

 描述(申请人提供)：淋巴管可以通过压力驱动流动或主动泵送液体，必要时甚至可以逆重力。在正常生理学中，淋巴系统能够使用这些机制来有效和动态地维持组织液的动态平衡。然而，在一些疾病中，淋巴功能效率低下，导致组织浮肿和免疫反应减弱。由于控制淋巴功能的机制尚不清楚，我们目前还没有有效的治疗方法来恢复这些患者的淋巴功能。我们认为，淋巴的运输是由涉及钙离子通量和一氧化氮的互补机制控制的。我们将通过开发淋巴运输和组织流体动力学的计算模型来检验这一假设。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治疗浮肿和淋巴流动受损的新疗法。

 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.