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Browsing by Author "Halme, Aleksi"

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  • Halme, Aleksi (2023)
    Lymphangiogenesis is crucial for the formation of a fully functional lymphatic vasculature. Dysfunctional lymphatic vasculature is associated with many pathologies including lymphatic malformations, lymphedema, and inflammation. This thesis aimed to elucidate the function of the lymphatic endothelial cell expressed β1-integrin in postnatal lymphangiogenesis in mice. To investigate this, Itgb1 gene was conditionally deleted from the lymphatic vasculature of mouse pups at postnatal day two, using the Cre-Lox recombinase system. Ears of the mice were collected at postnatal day twenty-one, and immunostained for lymphatic vessel, mural cell, and extracellular matrix markers. Relative gene expression analysis was performed from whole ear lysates and isolated endothelial cells. Mice lacking Itgb1 gene presented a disorganized dermal lymphatic vascular network, characterized by dilated capillary and collecting vessels. Collecting vessel specification was abnormal showing persistent LYVE1 expression, lack of V-shaped lymphatic valves, and complete loss of smooth muscle cell coverage. Relative gene expression analysis of isolated endothelial cells revealed a decrease in Pdgfb, a gene associated with smooth muscle cell recruitment. These results indicate a significant role for β1-integrin in postnatal lymphangiogenesis and highlight the complexity of postanal lymph vessel formation. Nevertheless, further studies are needed to specify the mechanisms behind this phenotype. Increasing knowledge in this field is important, because pathologies related to lymphangiogenesis can cause debilitating symptoms and therefore there is a need for therapeutic options.