VEGFR-3 in primary lymphedema
نویسندگان
چکیده
...............................................................................................................4 REVIEW OF THE LITERATURE ..............................................................................5 1 Development of the circulatory system.............................................................5 1.1 Vasculogenesis and angiogenesis .............................................................................. 5 1.2 Growth factors and receptors involved in angiogenesis ............................................. 6 1.2.1 Mechanisms of receptor tyrosine kinase signaling ........................................................6 1.2.2 VEGFs and their receptors .............................................................................................7 1.2.3 Angiopoietins and Tie receptors...................................................................................10 1.2.4 Ephrins..........................................................................................................................11 2 Lymphangiogenesis ...........................................................................................12 2.1 Formation and function of the lymphatic system ...................................................... 12 2.2 VEGFR-3 and its ligands in lymphangiogenesis....................................................... 13 2.3 Other lymphatic endothelial specific factors.............................................................. 15 2.3.1 Prospero-related homeobox protein 1 (Prox1).............................................................15 2.3.2 Podoplanin ....................................................................................................................16 2.3.3 Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1)...................................16 3 Diseases associated with RTK dysfunction ...................................................17 3.1 Lymphedema.............................................................................................................. 17 3.1.1 Pathophysiology of lymphedema .................................................................................17 3.1.2 Classification of lymphedema.......................................................................................17 3.1.3 Genetic alterations in lymphedema..............................................................................18 3.2 Inactivating RTK mutations in human syndromes .................................................... 20 4 Gene therapy .......................................................................................................21 4.1 Vectors and approaches............................................................................................ 21 4.2 Gene therapy in ECs.................................................................................................. 22 AIMS OF THIS STUDY............................................................................................24 MATERIALS AND METHODS................................................................................25 RESULTS AND DISCUSSION................................................................................27 1 The VEGFR3 genomic structure and regulatory region (I) ...........................27 2 Analysis of the lymphedema-linked mutant VEGFR-3s (II, III) .....................28 2.1 Dominant negative effect of the mutant VEGFR-3s.................................................. 28 2.2 Interaction of VEGFR-3 with other pathways............................................................ 30 3 The Chy mouse model for human primary lymphedema (IV).......................31 4 Lymphedema therapy in the Chy model (IV)...................................................32 CONCLUDING REMARKS .....................................................................................35 ACKNOWLEDGEMENTS .......................................................................................36 REFERENCES.........................................................................................................37
منابع مشابه
Serum level of VEGF-D in patients with primary lymphedema.
Recent studies have indicated that vascular endothelial growth factor-D (VEGF-D) stimulates lymphangiogenesis in humans. Furthermore, mutations of vascular endothelial growth factor receptor 3 (VEGFR-3) have been observed in families with hereditary lymphedema. The lack of stimulation of lymphangiogenesis could lead to production of even more VEGF-D to obtain stimulation of lymphangiogenesis re...
متن کاملThe resolution of lymphedema by interstitial flow in the mouse tail skin.
Lymphangiogenesis is considered a promising approach for increasing fluid drainage during secondary lymphedema. However, organization of lymphatics into functional capillaries may be dependent upon interstitial flow (IF). The present study was undertaken to determine the importance of lymphangiogenesis for lymphedema resolution. We created a lymphatic obstruction that produces lymphedema in mou...
متن کاملPrimary Congenital Lymphedema in the Upper Limbs of Children: Case Series
The aim of the present study was to report a case series involving the treatment of primary congenital lymphedema using the Godoy method. Eight children (seven girls and one boy) with primary congenital lymphedema of the upper limbs treated at the Godoy Clinic. A retrospective clinical trial was conducted to evaluate treatment for primary congenital l...
متن کاملIncreased interstitial protein because of impaired lymph drainage does not induce fibrosis and inflammation in lymphedema.
OBJECTIVE The pathophysiology of lymphedema is incompletely understood. We asked how transcapillary fluid balance parameters and lymph flow are affected in a transgenic mouse model of primary lymphedema, which due to an inhibition of vascular endothelial growth factor receptor-3 (VEGFR-3) signaling lacks dermal lymphatics, and whether protein accumulation in the interstitium occurring in lymphe...
متن کاملMilroy disease and the VEGFR-3 mutation phenotype.
Primary congenital lymphoedema (Milroy disease) is a rare autosomal dominant condition for which a major causative gene defect has recently been determined. Mutations in the vascular endothelial growth factor receptor 3 (VEGFR-3) gene have now been described in 13 families world-wide. This is a review of the condition based on the clinical findings in 71 subjects from 10 families. All 71 indivi...
متن کامل