Nox1 regulates apoptosis and potentially stimulates branching morphogenesis in sinusoidal endothelial cells.
Tubulogenic transformation of a nontubulogenic endothelial cell line NP31 by a constitutively activated form of the Flt-1 kinase (NP31/kinase) was accompanied by an increased expression of Nox1 by sixfold over NP31. Overexpression of Nox1 in NP31 cells (NP31/Nox1) stimulated branching morphogenesis in Matrigel but surprisingly cords lacked a lumen. The branching morphogenesis by NP31/kinase and NP31/Nox1 cells was blocked either by N-acetyl-l-cysteine (NAC) or Tiron. Vascular endothelial growth factor (VEGF)-dependent sinusoidal endothelial cells (SEC) in primary culture showed fivefold increase in Nox1 expression 4 days after VEGF stimulation. Interestingly, VEGF-resistant apoptosis in SEC at day 7 was inhibited by NAC or by anti-Nox1 siRNA. These results suggest that Nox1 regulates apoptosis in SEC and can potentially stimulate branching morphogenesis in SEC-derived NP 31 cells.
Department of Genetics, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-0071, Japan.
Satsuki
S
Kobayashi
Yoshihisa
Y
Nojima
Masabumi
M
Shibuya
Yoshiro
Y
Maru
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000502:physiology*; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D051843:Synucleins; D014162:Transfection; D040281:Vascular Endothelial Growth Factor Receptor-1
D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051843:Synucleins; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human; C501162:FLT1 protein, human; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1