Hypoxia stimulates the expression of macrophage migration inhibitory factor in human vascular smooth muscle cells via HIF-1alpha dependent pathway.
Hypoxia stimulates the expression of macrophage migration inhibitory factor in human vascular smooth muscle cells via HIF-1alpha dependent pathway.
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缺氧通过HIF-1α依赖性途径刺激人血管平滑肌细胞中巨噬细胞迁移抑制因子的表达。
DOI：
10.1186/1471-2121-11-66
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发表时间：
2010-08-20
期刊：
影响因子：
--
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Fu H;Luo F;Yang L;Wu W;Liu X
低氧在血管重塑中起重要作用，直接影响血管平滑肌细胞(VSMC)的功能。巨噬细胞移动抑制因子(MIF)是一种广为人知的促炎因子，最近的研究表明MIF在动脉粥样硬化和再狭窄的发展过程中起着重要作用。然而，VSMC中缺氧和MIF之间的潜在联系尚未被研究。本研究旨在检测缺氧是否能调节人VSMC中MIF的表达。同时研究MIF表达调控对缺氧诱导的VSMC增殖和迁移的影响。在中度低氧条件下(3%O2)培养的人VSMCs，MIF基因和蛋白的表达最早在2小时内上调。MIF表达的上调似乎依赖于缺氧诱导转录因子-1α(HIF-1α)，因为HIF-1α的敲除抑制了缺氧诱导的MIF基因和蛋白的表达。低氧诱导的MIF表达可通过抗氧化剂处理和抑制细胞外信号调节激酶(ERK)来减弱。在中度低氧条件下(3%O2)，VSMC细胞的增殖和迁移能力均增强。通过对MIF特异的小干扰RNA(MIF-shRNA)阻断MIF，可抑制VSMCs的增殖和迁移。我们的结果表明，在VSMC中，缺氧增加了MIF基因的表达和蛋白的产生。缺氧诱导的HIF-1α激活、ROS生成和ERK激活可能参与了这一反应。巨噬细胞生长因子和缺氧诱导因子-1α均介导血管平滑肌细胞的缺氧反应，包括细胞迁移和增殖。
Hypoxia plays an important role in vascular remodeling and directly affects vascular smooth muscle cells (VSMC) functions. Macrophage migration inhibitory factor (MIF) is a well known proinflammatory factor, and recent evidence suggests an important role of MIF in the progression of atherosclerosis and restenosis. However, the potential link between hypoxia and MIF in VSMC has not been investigated. The current study was designed to test whether hypoxia could regulate MIF expression in human VSMC. The effect of modulating MIF expression on hypoxia-induced VSMC proliferation and migration was also investigated at the same time. Expression of MIF mRNA and protein was up-regulated as early as 2 hours in cultured human VSMCs after exposed to moderate hypoxia condition (3% O2). The up-regulation of MIF expression appears to be dependent on hypoxia-inducible transcription factor-1α(HIF-1α) since knockdown of HIF-1α inhibits the hypoxia induction of MIF gene and protein expression. The hypoxia induced expression of MIF was attenuated by antioxidant treatment as well as by inhibition of extracellular signal-regulated kinase (ERK). Under moderate hypoxia conditions (3% O2), both cell proliferation and cell migration were increased in VSMC cells. Blocking the MIF by specific small interference RNA to MIF (MIF-shRNA) resulted in the suppression of proliferation and migration of VSMCs. Our results demonstrated that in VSMCs, hypoxia increased MIF gene expression and protein production. The hypoxia-induced HIF-1α activation, reactive oxygen species (ROS) generation and ERK activation might be involved in this response. Both MIF and HIF-1α mediated the hypoxia response of vascular smooth muscle cells, including cell migration and proliferation.
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影响因子：
3.7
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