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Browsing by Subject "VANGL2"

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  • Jakobsson, Emma (2023)
    The lymphatic system is a network of vessels that permeate a substantial part of the whole body. It plays an essential role in fluid homeostasis by the drainage of interstitial fluid from the blood capillaries, after which the fluid, now called lymph, is transported through the vessel network and back to the blood circulation. The lymphatic system also plays an important role in the transportation of immune cells and in activation and maintenance of the immune system. Due to these crucial functions, there is a growing interest in exploiting the lymphatic system in the treatment of many immunological and inflammatory diseases. In many cases, an ideal treatment method would be to induce lymphatic growth (lymphangiogenesis) to boost immunological functions, facilitate resolution of inflammation and reduce the harm from lymphatic vascular abnormalities. However, there is a gap in knowledge in how to induce lymphangiogenesis in a controlled manner, with the major lymphangiogenic growth factor, vascular endothelial factor C (VEGF-C), tending to create disorganized lymphatic networks. The purpose of this thesis is to investigate factors influencing lymphangiogenesis, in an attempt to find ways to control it. Vaahtomeri research group has preliminary results showing a role of planar cell polarity (PCP) in control of dermal lymphatic vessel sprouting (the initial step for the formation of new lymphatic branches) and lymphatic network expansion. The focus of Vaahtomeri research group has been the core PCP protein Van Gogh-like protein 2 (VANGL2), which together with the other core PCP proteins is known to play an important role in the collective cell polarization and morphogenesis in many tissue types. The role of VANGL2 has previously been studied in the lymphatic system, and so far, VANGL2 has been implicated in both lymphatic valve morphogenesis and in flow-induced control of lymphatic endothelial cell (LEC) polarization. However, there still remains a gap in knowledge in what role VANGL2 plays in lymphangiogenesis and the lymphatic network as a whole. In this thesis, I investigated the role of VANGL2 in lymphangiogenesis, firstly by the use of an in vivo lymph node experiment, which offered a robust model to investigate the role of VANGL2 in the mature lymph node lymphatic network. In the experiment, I induced growth of the lymph node lymphatic network by means of an immunization reaction, and then I compared the lymphatic networks of Vangl2-deleted and control mice. Despite some minor differences between the Vangl2-deleted and control lymphatic networks, this experiment did not show a role for VANGL2 in the mature lymph node lymphatic network. Secondly, I investigated the potential mechanistic role of VANGL2 in control of dermal lymphatic vessel sprouting in growth conditions. This experiment showed a specific role for VANGL2 in sprouting of the lymphatic network, thus providing valuable research in understanding how lymphangiogenesis is regulated. Altogether, the results presented in this thesis work as a steppingstone for finding new treatments relating to the safe induction of lymphangiogenesis.