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Browsing by Subject "VEGF-C"

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  • Tiilikainen, Emmi (2023)
    Lymphatic vascular system consists of lymphatic capillaries and collectors existing alongside a circulatory system of blood vessels. The lymphatic system is responsible of draining tissue fluids, trafficking of immune cells and intestinal absorption of dietary lipids. Most of the lymphatic networks develop during embryogenesis, but lymphangiogenesis (the growth of new lymphatic vessel, LV) occurs also in adult tissues, for example, during inflammation. Exposure to vascular endothelial growth factor C (VEGF-C) initiates lymphatic endothelial cell (LEC) proliferation and sprouting of LVs. In lymphangiogenesis, leading tip cell migrates and samples the surrounding environment while stalk cells proliferate and are responsible of LV elongation and extension. Since polarity of dividing cells and subsequent daughter cell positioning possess a key role in morphogenesis of tubular organs, such as lungs, kidney or blood vessels, a regulation of daughter LEC positioning after cell division might determine how LVs elongate and widen. The aim of this study was to investigate the LV network enlargement and daughter LEC positioning during growth of LVs and to reveal potential contributing factors guiding the cell positioning (such as cell polarity). In this study, the LV network of mouse ear pinna was used as a model tissue to investigate LV network enlargement, daughter LEC positioning and LEC polarity in growing LVs. Characterization of mitotic cells in developing LV network revealed that LEC proliferation occurs throughout the entire length of LVs in the network. To investigate LEC polarity in developing and mature LVs, I analysed Golgi and nuclear polarity of tip and stalk LECs. I found that whereas LECs during development are polarized and oriented along the long axis of LV, there is more variation in the direction of LEC polarity in relation to LV long axis in mature LV. This observation raised a question whether changes in the cell polarity were reflected to cell positioning, hence I analysed the positioning of daughter LECs by forcing LECs to the cell cycle with VEGF-C. These results indicated cell-level mechanisms that may contribute to LEC positioning in lymphangiogenesis. My finding provides an efficient tool for further research due to its suitability for monitoring proliferating LECs and studying causative factors affecting LEC proliferation and positioning. Future experiments with real-time imaging will reveal more about lymphangiogenesis process and provide insights into the role of lymphatic vasculature in conditions such as inflammation-related lymphedema or anti-tumor immunity in cancer.