Defining the role of lymphatic vessels in wound healing

我的实验室最近发现了一个意想不到的和有趣的作用淋巴管在皮肤伤口 治愈特别是，我们发现没有淋巴管的小鼠表现出血管再生过度， 损伤后纤维化我们的发现很重要，原因有几个。首先，虽然淋巴管已经 虽然这些细胞对皮肤修复很重要，但人们对它们在皮肤修复中的确切功能知之甚少。 其次，我们的数据揭示了涉及淋巴管的未知机制控制血管修复， 皮肤纤维化，这两种情况影响伤口愈合和过度瘢痕形成。最后，慢性水肿， 使人衰弱和无法治愈的肿胀，这可能是由于淋巴管系统受损所致， 手术、癌症、治疗或伤害影响着超过1000万美国人。通过这些重点和 互补的特定目的，在本申请中提出的工作将利用多个遗传 允许淋巴管特异性耗竭的小鼠模型、最新基因组学、细胞培养模型。 我们将（1）确定在淋巴管内皮细胞中驱动淋巴管内皮再生的细胞和分子机制， （2）分析淋巴管内皮细胞在抑制血管修复中的功能， 有助于纤维化，以及（3）确定增强淋巴管修复是否改善缺陷性伤口 老年和糖尿病小鼠。这些研究将确定特定的促愈合细胞和分子机制， 可用于促进具有缺陷性伤口愈合或淋巴疾病的人类患者的愈合。

My laboratory recently uncovered an unexpected and intriguing role for a lymphatic vessels during skin wound healing. In particular, we identified that mice without lymphatic vessels display hypervascular regeneration and fibrosis after injury. Our findings are important for several reasons. First, while lymphatic vessels have been shown to be important for skin repair, the precise function of these cells in skin repair is poorly understood. Second, our data reveal that unknown mechanisms involving lymphatic vessels control blood vessel repair and skin fibrosis, two conditions that impact wound healing and excessive scarring. Finally, lymphedema, a chronic, debilitating and incurable swelling that can be a result of damage to the lymphatic vessel system due to surgery, cancer, treatments, or injury, affects over 10 million Americans. Through these focused and complementary Specific Aims, the work proposed in this application will take advantage of multiple genetic mouse models that allow specific depletion of lymphatic vessels, state of the art genomics, cell culture models. We will (1) identify the cellular and molecular mechanisms that drive lymphatic endothelial regeneration in the skin, (2) analyze the function of lymphatic endothelium cells in suppressing blood vessel repair and contributing to fibrosis, and (3) define whether enhancing lymphatic vessel repair ameliorates defective wounds of aged and diabetic mice. These studies will identify specific pro-healing cells and molecular mechanisms that can be utilized to promote healing in human patients with defective wound healing or lymphatic disorders.