Role and mechanism of arsenic in regulating angiogenesis.
Role and mechanism of arsenic in regulating angiogenesis.
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DOI：
10.1371/journal.pone.0020858
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Jiang BH
中科院分区：
文献类型：
--
作者：
Liu LZ;Jiang Y;Carpenter RL;Jing Y;Peiper SC;Jiang BH
砷是一种广泛传播的致癌物质，与几种癌症有关，包括皮肤癌、肺癌、膀胱癌和肝癌。肺是砷暴露的主要靶点之一。血管生成是肺癌发生和慢性肺疾病的关键过程，但砷对血管生成的调控作用及其机制尚不清楚。在这项研究中，我们表明，砷短时间暴露诱导血管生成的人永生化肺上皮细胞BEAS-2B和腺癌细胞A549。为了研究砷诱导血管生成的分子机制，我们发现砷诱导活性氧（ROS）的产生，从而激活AKT和ERK 1/2信号通路，并增加缺氧诱导因子1（HIF-1）和血管内皮生长因子（VEGF）的表达。抑制ROS产生通过降低AKT和ERK活化以及HIF-1表达来抑制血管生成。抑制ROS、AKT和ERK 1/2信号通路足以减弱砷诱导的血管生成。HIF-1和VEGF是砷诱导血管生成所需的AKT和ERK 1/2的下游效应物。这些结果揭示了砷调节血管生成的机制，并有助于发展基于机制的干预，以防止砷诱导的致癌和血管生成的未来。
Arsenic is a wide spread carcinogen associated with several kinds of cancers including skin, lung, bladder, and liver cancers. Lung is one of the major targets of arsenic exposure. Angiogenesis is the pivotal process during carcinogenesis and chronic pulmonary diseases, but the role and mechanism of arsenic in regulating angiogenesis remain to be elucidated. In this study we show that short time exposure of arsenic induces angiogenesis in both human immortalized lung epithelial cells BEAS-2B and adenocarcinoma cells A549. To study the molecular mechanism of arsenic-inducing angiogenesis, we find that arsenic induces reactive oxygen species (ROS) generation, which activates AKT and ERK1/2 signaling pathways and increases the expression of hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF). Inhibition of ROS production suppresses angiogenesis by decreasing AKT and ERK activation and HIF-1 expression. Inhibition of ROS, AKT and ERK1/2 signaling pathways is sufficient to attenuate arsenic-inducing angiogenesis. HIF-1 and VEGF are downstream effectors of AKT and ERK1/2 that are required for arsenic-inducing angiogenesis. These results shed light on the mechanism of arsenic in regulating angiogenesis, and are helpful to develop mechanism-based intervention to prevent arsenic-induced carcinogenesis and angiogenesis in the future.
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影响因子：
10.4
作者：
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影响因子：
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发表时间：
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