Members of the Jagged/Notch gene families are expressed in injured arteries and regulate cell phenotype via alterations in cell matrix and cell-cell interaction
Members of the Jagged/Notch gene families are expressed in injured arteries and regulate cell phenotype via alterations in cell matrix and cell-cell interaction
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DOI：
10.1016/s0002-9440(10)61763-4
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发表时间：
2001-09-01
影响因子：
6
通讯作者：
Liaw, L
中科院分区：
文献类型：
--
作者：
Lindner, V;Booth, C;Liaw, L
Jagged/Notch 信号通路控制细胞命运决定和分化，其功能障碍与涉及心血管异常的人类病理有关。为了确定这些基因在血管对损伤的反应过程中是否存在，我们分析了大鼠颈动脉球囊导管剥脱后 Jagged1、Jagged2 和 Notch1 至 4 的表达。尽管在未损伤的内皮细胞中观察到 Jagged1、Jagged2 和 Notch1 的组成型表达水平较低，但在损伤的血管细胞中所有表达均显着增加。 Jagged1 的高表达仅限于再生内皮伤口边缘，而 Notch 转录物在内皮细胞和平滑肌细胞中丰富。为了了解 Jagged/Notch 控制细胞表型的基础，我们研究了用分泌形式的 Jagged1 胞外结构域转染的 NIH3T3 细胞的体外模型。我们报告可溶性 Jagged1 蛋白导致细胞基质粘附力下降和细胞迁移缺陷。钙粘蛋白介导的细胞间连接以及粘着斑在可溶性 Jagged1 转染子中被修饰，证明细胞-细胞接触和粘附斑可能是 Jagged/Notch 活性的目标。我们认为，细胞-细胞和细胞-基质相互作用的锯齿状调节可能有助于体内组织重塑情况下细胞迁移的控制。
The Jagged/Notch signaling pathways control cell fate determination and differentiation, and their dysfunction is associated with human pathologies involving cardiovascular abnormalities. To determine the presence of these genes during vascular response to injury, we analyzed expression of Jagged1, Jagged2, and Notch1 through 4 after balloon catheter denudation of the rat carotid artery. Although low levels of Jagged1, Jagged2, and constitutive expression of Notch1 were seen in uninjured endothelium, expression of all was significantly increased in injured vascular cells. High Jagged1 expression was restricted to the regenerating endothelial wound edge, whereas Notch transcripts were abundant in endothelial and smooth muscle cells. To understand the basis for Jagged/Notch control of cellular phenotype, we studied an in vitro model of NIH3T3 cells transfected with a secreted form of the extracellular domain of Jagged1. We report that the soluble Jagged1 protein caused decreased cell-matrix adhesion and cell migration defects. Cadherin-mediated intercellular junctions as well as focal adhesions were modified in soluble Jagged1 transfectants, demonstrating that cell-cell contacts and adhesion plaques may be targets of Jagged/Notch activity. We suggest that jagged regulation of cell-cell and cell-matrix interactions may contribute to the control of cell migration in situations of tissue remodeling in vivo.