Browsing by Author "Saari, Jeremia"

Lymphatic vasculature lines densely the outer borders of the body, such as the skin, the lungs, and the gut. The peripheral lymphatic system drains interstadial fluid from tissues and returns it to circulation. In turn, poor lymphatic vascularization of tissue causes swelling, i. e. lymphedema, and has been linked to worsened inflammation resolution, and heightened reoccurrence of Crohn’s disease. In colorectal cancer, lymphatic invasion to the tumor margin can either improve or worsen prognosis, depending on anti-tumor immune response or the lack thereof. Association with pathological conditions such as these drives research into developmental and post-developmental lymphatic growth. The most important growth factor for lymphatic endothelium is VEGF-C. The exposure of mature lymphatics to VEGF-C increases vascular density by inducing growth of new branches but the details of this “sprouting lymphangiogenesis” are not completely understood. One important effector in lymphatic endothelium is VE-cadherin, an adhesion molecule found in endothelial cell junctions. VE-cadherin plays a role in endothelial permeability, integrity, and suppression of VEGF-C signaling. This thesis includes the characterization of subcellular VE-cadherin localization in sprouting lymphatic endothelium via immunofluorescence microscopy. Subsequently, the role of VE-cadherin in sprouting lymphatic endothelium was functionally validated. Research into lymphatic sprouting is motivated not only by the prospect of gaining insight into vascular development but translational potential. While VEGF-C has been used to induce lymphatic growth in a therapeutical context, its potency as a growth-stimulating compound results in unpredictable and chaotic network expansion. Exploration into the molecular regulators of lymphatic sprouting aims to reveal new therapeutical targets for harnessing the peripheral lymphatics against inflammation-related disease, with precision.