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Title: Signalling interactions between platelets and lymphatic endothelial cells, linked to lymphangiogenesis
Author: Langan, Stacey Anne
ISNI:       0000 0004 5367 6354
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2015
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The platelet receptor CLEC-2 is the only known endogenous ligand for the transmembrane receptor podoplanin, which is expressed on lymphatic endothelial cells (LEC) as well as a number of other cell types. Both CLEC-2 and podoplanin are required for normal lymphangiogenesis as mouse embryos lacking either protein develop a phenotype in which blood is detected in the lymphatic vessels. This thesis examines the role of the podoplanin-CLEC-2 interaction in the migratory and tube-forming capabilities of LEC. Addition of platelets or antibody-mediated podoplanin crosslinking both inhibited migration of LEC in transfilter migration assays in the presence, but not absence, of vascular endothelial growth factor (VEGF)-C. Similarly, platelets and podoplanin crosslinking reduced stability of LEC networks formed in co-cultures with fibroblasts. We also found that siRNA-mediated knockdown of podoplanin negated the pro-migratory effects of VEGF-C and VEGF-A. Furthermore, we obtained evidence that podoplanin signalling may involve RhoA and Rho-kinase, and that the effect of podoplanin might be linked to its phosphorylation by protein kinase A downstream of VEGF receptor signalling. These data suggest that the interaction of podoplanin and CLEC-2 prevents connection between blood and lymphatic vessels through reductions in LEC migration and stability of cell-cell interactions.
Supervisor: Not available Sponsor: Medical Research Council (MRC) ; British Heart Foundation (BHF)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RB Pathology ; RC Internal medicine