Dysregulation of Lymphatic Endothelial VEGFR3 Signaling in Disease.
Kevin KuonquiAdana-Christine CampbellAnanta SarkerArielle RobertsBracha L PollackHyeung Ju ParkJinyeon ShinStav BrownBabak J MehraraRaghu P KataruPublished in: Cells (2023)
Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR3), a receptor tyrosine kinase encoded by the FLT4 gene, plays a significant role in the morphogenesis and maintenance of lymphatic vessels. Under both normal and pathologic conditions, VEGF-C and VEGF-D bind VEGFR3 on the surface of lymphatic endothelial cells (LECs) and induce lymphatic proliferation, migration, and survival by activating intracellular PI3K-Akt and MAPK-ERK signaling pathways. Impaired lymphatic function and VEGFR3 signaling has been linked with a myriad of commonly encountered clinical conditions. This review provides a brief overview of intracellular VEGFR3 signaling in LECs and explores examples of dysregulated VEGFR3 signaling in various disease states, including (1) lymphedema, (2) tumor growth and metastasis, (3) obesity and metabolic syndrome, (4) organ transplant rejection, and (5) autoimmune disorders. A more complete understanding of the molecular mechanisms underlying the lymphatic pathology of each disease will allow for the development of novel strategies to treat these chronic and often debilitating illnesses.
Keyphrases
- vascular endothelial growth factor
- signaling pathway
- endothelial cells
- pi k akt
- lymph node
- tyrosine kinase
- metabolic syndrome
- cell proliferation
- induced apoptosis
- epithelial mesenchymal transition
- insulin resistance
- high glucose
- epidermal growth factor receptor
- type diabetes
- multiple sclerosis
- copy number
- neoadjuvant chemotherapy
- squamous cell carcinoma
- cardiovascular disease
- weight loss
- adipose tissue
- oxidative stress
- body mass index
- skeletal muscle
- cell death
- weight gain