Vascular Endothelial Cell Growth Factor A Acts via Platelet-Derived Growth Factor Receptor α To Promote Viability of Cells Enduring Hypoxia.
Vascular endothelial cell growth factor A (VEGF) is a biologically and therapeutically important growth factor because it promotes angiogenesis in response to hypoxia, which underlies a wide variety of both physiological and pathological settings. We report here that both VEGF receptor 2 (VEGFR2)-positive and -negative cells depended on VEGF to endure hypoxia. VEGF enhanced the viability of platelet-derived growth factor receptor α (PDGFRα)-positive and VEGFR2-negative cells by enabling indirect activation of PDGFRα, thereby reducing the level of p53. We conclude that the breadth of VEGF's influence extends beyond VEGFR-positive cells and propose a plausible mechanistic explanation of this phenomenon.
The Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
Steven
S
Pennock
The Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
Leo A
LA
Kim
The Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA andrius_kazlauskas@meei.harvard.edu.
Andrius
A
Kazlauskas
D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival; D005347:Fibroblasts / Q000166:cytology*; D051379:Mice; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C501163:Flt1 protein, mouse; C000592875:Kdr protein, mouse; D020796:Receptor, Platelet-Derived Growth Factor alpha; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2