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Pim-3在内皮细胞中表达并促进血管管形成。

Pim-3 is expressed in endothelial cells and promotes vascular tube formation.

作者信息

Zhang Peng, Wang Hanqin, Min Xinwen, Wang Yinfang, Tang Jie, Cheng Jishun, Li Dongfeng, Chen Xin, Cheng Fanjun, Wang Nanping, Yang Handong

机构信息

Institute of Cardiovascular Science, DongFeng Hospital, YunYang Medical College, Hubei, China.

出版信息

J Cell Physiol. 2009 Jul;220(1):82-90. doi: 10.1002/jcp.21733.

Abstract

Pim-3 is a member of proto-oncogene Pim family that encodes serine/threonine kinases. Pim proteins regulate both apoptosis and cellular metabolism by phosphorylating their substrates. Here, we report for the first time that Pim-3 is highly expressed at mRNA and protein levels in endothelial cells (ECs). We found that Pim-3 is concentrated at the cellular lamellipodia and co-localized with focal adhesion kinase (FAK). Pim-3 was dispersed from lamellipodia when ECs were treated with cytochalasin D, an inhibitor of actin polymerization. In addition, small-interfering RNA (siRNA)-mediated gene knockdown of Pim-3 significantly impaired EC spreading, migration, and proliferation, leading to a reduction in tube-like structure formation in a Matrigel assay. These results provide the novel evidence that Pim-3 plays an essential role in EC spreading and migration, suggesting that Pim-3 may be an important molecular target for the development of small-molecule inhibitors of angiogenesis.

摘要

Pim-3是原癌基因Pim家族的成员,该家族编码丝氨酸/苏氨酸激酶。Pim蛋白通过磷酸化其底物来调节细胞凋亡和细胞代谢。在此,我们首次报道Pim-3在内皮细胞(ECs)的mRNA和蛋白水平上高表达。我们发现Pim-3集中在细胞片状伪足处,并与粘着斑激酶(FAK)共定位。当用细胞松弛素D(一种肌动蛋白聚合抑制剂)处理ECs时,Pim-3从片状伪足处分散。此外,小干扰RNA(siRNA)介导的Pim-3基因敲低显著损害了EC的铺展、迁移和增殖,导致在基质胶试验中管状结构形成减少。这些结果提供了新的证据,表明Pim-3在EC铺展和迁移中起重要作用,提示Pim-3可能是开发血管生成小分子抑制剂的重要分子靶点。

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