Nox1 regulates apoptosis and potentially stimulates branching morphogenesis in sinusoidal endothelial cells |
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Authors: | Kobayashi Satsuki Nojima Yoshihisa Shibuya Masabumi Maru Yoshiro |
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Affiliation: | Department of Genetics, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-0071, Japan. |
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Abstract: | 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. |
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Keywords: | Nox1 Oxidase Endothelial cells Flt-1 Vascular endothelial growth factor |
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