Expression of vascular endothelial growth factor receptor 1 in bone marrow-derived mesenchymal cells is dependent on hypoxia-inducible factor 1
Expression of vascular endothelial growth factor receptor 1 in bone marrow-derived mesenchymal cells is dependent on hypoxia-inducible factor 1
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DOI：
10.1074/jbc.m602003200
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发表时间：
2006-06-02
影响因子：
4.8
通讯作者：
Semenza, Gregg L.
中科院分区：
文献类型：
--
作者：
Okuyama, Hiroaki;Krishnamachary, Balaji;Semenza, Gregg L.
骨髓来源的细胞被招募到缺血部位，在那里它们促进组织血管形成。这种反应依赖于血管内皮生长因子受体1(VEGFR1)的表达，VEGFR1介导细胞对血管内皮生长因子或胎盘生长因子(PLGF)的反应。在这项研究中，我们发现，培养的小鼠骨髓间充质干细胞(MSC)暴露于低氧或低氧诱导因子1(HIF-1)的腺病毒中，可诱导VEGFR1mRNA和蛋白的表达，并促进血管内皮生长因子(VEGF)或PLGF的体外迁移。通过显性阴性或RNA干扰方法抑制HIF-1活性的MSCs表达VEGFR1水平显著降低，并且不能迁移或激活AKT以响应血管内皮生长因子或PLGF。因此，功能丧失和功能获得的方法表明，HIF-1活性是基础和低氧诱导的骨髓间充质干细胞表达VEGFR1的必要条件和充分条件。
Bone marrow-derived cells are recruited to sites of ischemia, where they promote tissue vascularization. This response is dependent upon the expression of vascular endothelial growth factor ( VEGF) receptor 1 ( VEGFR1), which mediates cell migration in response to VEGF or placental growth factor ( PLGF). In this study, we found that exposure of cultured mouse bone marrow-derived mesenchymal stromal cells ( MSC) to hypoxia or an adenovirus encoding a constitutively active form of hypoxia-inducible factor 1 ( HIF-1) induced VEGFR1 mRNA and protein expression and promoted ex vivo migration in response to VEGF or PLGF. MSCin which HIF-1 activity was inhibited by a dominant negative or RNA interference approach expressed markedly reduced levels of VEGFR1 and failed to migrate or activate AKT in response to VEGF or PLGF. Thus, loss-of-function and gain-of-function approaches demonstrated that HIF-1 activity is necessary and sufficient for basal and hypoxia-induced VEGFR1 expression in bone marrow-derived MSC.