Date of Award

2019

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Cell & Molecular Biology

First Advisor

Mark L. Kahn

Abstract

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.

Embargoed

Available to all on Tuesday, January 10, 2023

Files over 3MB may be slow to open. For best results, right-click and select "save as..."

Share

COinS