title: The angiogenic factor Del1 prevents apoptosis of endothelial cells through integrin binding.
abstract: BACKGROUND
  Del1 is a secreted protein that is expressed in the endothelium during development and can stimulate angiogenesis through integrin binding and signaling. We were interested in the specific effects of del1 on endothelial cell biology to gain insight into its biologic role during angiogenesis.
  
  
  METHODS
  Primary endothelial cells were treated with a variety of inducers of apoptosis and anoikis followed by assays for numbers of apoptotic cells, and harvest of total protein for immunoblot analysis.
  
  
  RESULTS
  Del1 prevented endothelial cell apoptosis in response to TNFα/IFNγ, etoposide, and anoikis, but had no effect on proliferation. The anti-apoptotic effect was mediated specifically through binding of integrin αvβ3 by the RGD motif. FAK/ERK and Akt signaling were both necessary to mediate the anti-apoptotic effect of Del1 with the exception of anoikis, which required only Akt activation.
  
  
  CONCLUSIONS
  Del1 has been previously shown to promote vascular smooth muscle cell adhesion, migration, and proliferation. We demonstrate here that Del1 prevented apoptosis of endothelial cells in cell culture through integrin binding without any effect on proliferation.
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
authors: Zhen
authors: Z
authors: Wang
authors: Ramendra K
authors: RK
authors: Kundu
authors: Michael T
authors: MT
authors: Longaker
authors: Thomas
authors: T
authors: Quertermous
authors: George P
authors: GP
authors: Yang
mesh_terms: D023102:Anoikis / Q000187:drug effects / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000494:pharmacology*; D015815:Cell Adhesion Molecules; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C110183:EDIL3 protein, human; D039302:Integrin alphaVbeta3; D014409:Tumor Necrosis Factor-alpha; D005047:Etoposide; D007371:Interferon-gamma