Kobayashi Satsuki, Nojima Yoshihisa, Shibuya Masabumi, Maru Yoshiro
Department of Genetics, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-0071, Japan.
Exp Cell Res. 2004 Nov 1;300(2):455-62. doi: 10.1016/j.yexcr.2004.07.023.
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.
通过组成型激活形式的Flt-1激酶（NP31/激酶）将非成管内皮细胞系NP31诱导成管转化，伴随着Nox1的表达比NP31增加了六倍。在NP31细胞（NP31/Nox1）中过表达Nox1可刺激基质胶中的分支形态发生，但令人惊讶的是，形成的索状结构缺乏管腔。NP31/激酶和NP31/Nox1细胞的分支形态发生被N-乙酰-L-半胱氨酸（NAC）或钛铁试剂阻断。原代培养中血管内皮生长因子（VEGF）依赖性的肝血窦内皮细胞（SEC）在VEGF刺激4天后，Nox1表达增加了五倍。有趣的是，NAC或抗Nox1 siRNA可抑制第7天SEC中VEGF抗性凋亡。这些结果表明，Nox1调节SEC中的凋亡，并可能潜在地刺激SEC来源的NP 31细胞中的分支形态发生。
