Date of Award
Doctor of Philosophy (PhD)
Cell & Molecular Biology
Mark L. Kahn
The lymphatic system is a vascular system that is present throughout most organs of the body, and plays important roles in fluid homeostasis, lipid uptake in the intestines, as well as in immune cell trafficking and adipose metabolism. Vascular endothelial growth factor C (VEGFC) is the primary lymphangiogenic factor that stimulates lymphangiogenesis during development, signaling via its receptor vascular endothelial growth factor receptor 3 (VEGFR3). In the adult animal, lymphatic vessels are mostly quiescent, but wound healing that follows injury is often accompanied by lymphangiogenesis. The hemostatic response following injury brings platelets to the injury site that helps to stem bleeding, and subsequent fibrin clot formation helps to stabilize the clot. Here, using a novel tail injury assay, we showed that the hemostatic response mediates wound healing lymphangiogenesis by bringing VEGFC to the site of injury via platelets, and that thrombin, a serine protease present in injury sites, can cleave and activate VEGFC, elucidating novel roles for the hemostatic response in lymphangiogenesis. Together, these studies define a link between hemostasis and lymphangiogenesis, and reveal VEGFC to be the major lymphangiogenic factor in two different injury models.
Lim, Lillian, "Roles Of Vegfc And Vegfr3 In Lymphangiogenesis And Angiogenesis" (2019). Publicly Accessible Penn Dissertations. 3665.