Glienke Jens, Sturz Andrea, Menrad Andreas, Thierauch Karl Heinz
Experimental Oncology, Research Laboratories of Schering AG, Müllerstrasse 178, D-13342 Berlin, Germany.
Mech Dev. 2002 Dec;119(2):165-75. doi: 10.1016/s0925-4773(02)00355-6.
In endothelial cells that form capillary-like structures in vitro a variety of genes is upregulated as we have demonstrated previously. In addition to well known genes, we also identified genes never described in endothelial cells before. Here, we report the further characterization of one selected gene called cysteine-rich motor neuron 1 (CRIM1). CRIM1 is strongly upregulated in endothelial cells during tube formation and is expressed by a variety of adherent growing cell lines whereas cell lines grown in suspension do not express CRIM1. By using antisense technology we were able to inhibit CRIM1 expression and demonstrate impaired formation of capillary-like structures in vitro in transfected endothelial cells. Furthermore, we show that CRIM1 is a glycosylated type I transmembrane protein, that accumulates at sites of close cell-to-cell contact upon stimulation. Finally, we found CRIM1 protein to be expressed by endothelial cells of the inner lining of blood vessels in vivo. Taken together our results imply a possible role of CRIM1 in capillary formation and maintainance during angiogenesis.
正如我们之前所证明的,在体外形成毛细血管样结构的内皮细胞中,多种基因被上调。除了众所周知的基因外,我们还鉴定出了以前在内皮细胞中从未描述过的基因。在此,我们报告了一个名为富含半胱氨酸的运动神经元1(CRIM1)的选定基因的进一步特征。CRIM1在体外管形成过程中在内皮细胞中强烈上调,并且在多种贴壁生长的细胞系中表达,而悬浮生长的细胞系不表达CRIM1。通过使用反义技术,我们能够抑制CRIM1的表达,并证明在转染的内皮细胞中体外毛细血管样结构的形成受损。此外,我们表明CRIM1是一种糖基化的I型跨膜蛋白,在刺激后会在细胞间紧密接触的部位积累。最后,我们发现CRIM1蛋白在体内血管内层的内皮细胞中表达。综上所述,我们的结果暗示CRIM1在血管生成过程中的毛细血管形成和维持中可能发挥作用。