Normoxic induction of the hypoxic-inducible factor-1α by interleukin-1β involves the extracellular signal-regulated kinase 1/2 pathway in normal human cytotrophoblast cells
Normoxic induction of the hypoxic-inducible factor-1α by interleukin-1β involves the extracellular signal-regulated kinase 1/2 pathway in normal human cytotrophoblast cells
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DOI：
10.1095/biolreprod.103.025031
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发表时间：
2004-06-01
影响因子：
3.6
通讯作者：
Zhu, C
中科院分区：
文献类型：
--
作者：
Qian, D;Lin, HY;Zhu, C
在妊娠早期，相对低氧张力的环境对于正常的胚胎和胎盘血管系统是必不可少的。在低氧条件下，由α和β亚基组成的低氧诱导因子-1（HIF-1）控制许多基因的表达，如血管内皮生长因子（VEGF），一种关键的血管生成因子。近年来在一些肿瘤细胞中的研究发现，不稳定成分HIF-1 α不仅被缺氧激活，而且在常氧条件下也被白细胞介素-1（IL-1）等肽激活。在这篇文章中，我们证明了正常人细胞滋养层细胞暴露于IL-1 β刺激HIF-1 α蛋白的表达。同时，IL-1 β还诱导正常人细胞滋养层细胞分泌VEGF。我们的数据表明，IL-1 β诱导细胞外信号调节激酶（ERK）1/2磷酸化。此外，用ERK 1/2信号传导抑制剂PD 98059处理细胞，抑制IL-1 β对HIF-1 α蛋白表达和VEGF分泌的刺激。这些数据表明，在正常人细胞滋养层细胞中，IL-1 R诱导HIFI 1 α介导的VEGF分泌，IL-1 β刺激的ERK 1/2激活可能参与了这一过程。
During early pregnancy, an environment of relative low oxygen tension is essential for normal embryonic and placental vasculature. In low-oxygen conditions, the hypoxic-inducible factor-1 (HIF-1), composed of alpha and beta subunits, controls the expression of a number of genes such as vascular endothelial growth factor (VEGF), a key angiogenic factor. The recent studies in some tumor cells have found that the labile component, HIF-1alpha, is not only activated by hypoxia but also by peptides such as interieukin-1 (IL-1) in normoxia. In this article, we demonstrated that exposure of normal human cytotrophoblast cells to IL-Ibeta stimulated the expression of HIF-1alpha protein. Meanwhile, IL-1beta also induced the secretion of VEGF in normal human cytotrophoblast cells. Our data indicated that IL-1beta induced extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. Moreover, treatment of cells with PD98059, an inhibitor of ERK1/2 signaling, inhibited the stimulation of HIF-1alpha protein expression and VEGF secretion by IL-1beta. These data indicate that, in normal human cytotrophoblast cells, IL-1 R induces HIFI 1alpha-mediated VEGF secretion and that 1L-1beta-stimulated ERK1/2 activation may be involved in this process.