The role of VEGF 165b in pathophysiology.
Anti-angiogenic vascular endothelial growth factor A (VEGF) 165b and pro-angiogenic VEGF 165 are generated from the same transcript, and their relative amounts are dependent on alternative splicing. The role of VEGF 165b has not been investigated in as much detail as VEGF 165, although it appears to be highly expressed in non-angiogenic tissues and, in contrast with VEGF 165, is downregulated in tumors and other pathologies associated with abnormal neovascularization such as diabetic retinopathy or Denys Drash syndrome. VEGF 165b inhibits VEGFR2 signaling by inducing differential phosphorylation, and it can be used to block angiogenesis in in vivo models of tumorigenesis and angiogenesis-related eye disease. Recent reports have identified three serine/arginine-rich proteins, SRSF1, SRSF2 and SRSF6, and studied their role in regulating terminal splice-site selection. Since the balance of VEGF isoforms is lost in cancer and angiogenesis-related conditions, control of VEGF splicing could also be used as a basis for therapy in these diseases.
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
Maria
M
Peiris-Pagès
D017398:Alternative Splicing; D000818:Animals; D002199:Capillary Permeability; D030321:Denys-Drash Syndrome / Q000378:metabolism / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000503:physiopathology*; D005921:Glomerulonephritis / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D009687:Nuclear Proteins; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068103:Serine-Arginine Splicing Factors; D040301:Vascular Endothelial Growth Factor Receptor-2