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首页> 外文期刊>Journal of inflammation. >Cigarette smoke regulates VEGFR2-mediated survival signaling in rat lungs
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Cigarette smoke regulates VEGFR2-mediated survival signaling in rat lungs

机译：香烟烟雾调节大鼠肺中VEGFR2介导的生存信号

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Background Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2)-mediated survival signaling is critical to endothelial cell survival, maintenance of the vasculature and alveolar structure and regeneration of lung tissue. Reduced VEGF and VEGFR2 expression in emphysematous lungs has been linked to increased endothelial cell death and vascular regression. Previously, we have shown that CS down-regulated the VEGFR2 and its downstream signaling in mouse lungs. However, the VEGFR2-mediated survival signaling in response to oxidants/cigarette smoke (CS) is not known. We hypothesized that CS exposure leads to disruption of VEGFR2-mediated endothelial survival signaling in rat lungs. Methods Adult male Sprague-Dawley rats were exposed CS for 3 days, 8 weeks and 6 months to investigate the effect of CS on VEGFR2-mediated survival signaling by measuring the Akt/PI3-kinase/eNOS downstream signaling in rat lungs. Results and Discussion We show that CS disrupts VEGFR2/PI3-kinase association leading to decreased Akt and eNOS phosphorylation. This may further alter the phosphorylation of the pro-apoptotic protein Bad and increase the Bad/Bcl-xl association. However, this was not associated with a significant lung cell death as evidenced by active caspase-3 levels. These data suggest that although CS altered the VEGFR2-mediated survival signaling in the rat lungs, but it was not sufficient to cause lung cell death. Conclusion The rat lungs exposed to CS in acute, sub-chronic and chronic levels may be representative of smokers where survival signaling is altered but was not associated with lung cell death whereas emphysema is known to be associated with lung cell apoptosis.
机译：背景技术血管内皮生长因子（VEGF）和VEGF受体2（VEGFR2）介导的存活信号对于内皮细胞存活，维持脉管系统和肺泡结构以及肺组织再生至关重要。气肿性肺中VEGF和VEGFR2表达的降低与内皮细胞死亡和血管退化的增加有关。以前，我们已经显示CS在小鼠肺中下调了VEGFR2及其下游信号传导。但是，还不知道应答于氧化剂/香烟烟雾（CS）的VEGFR2介导的生存信号。我们假设CS暴露导致大鼠肺VEGFR2介导的内皮细胞生存信号的破坏。方法成年雄性Sprague-Dawley大鼠暴露于CS 3天，8周和6个月，通过测量大鼠肺中Akt / PI3-激酶/ eNOS下游信号传导来研究CS对VEGFR2介导的生存信号传导的影响。结果与讨论我们显示CS破坏了VEGFR2 / PI3-激酶缔合，导致Akt和eNOS磷酸化降低。这可以进一步改变促凋亡蛋白Bad的磷酸化并增加Bad / Bcl-xl缔合。但是，这与活跃的caspase-3水平所证明的肺细胞死亡无关。这些数据表明，尽管CS改变了大鼠肺中VEGFR2介导的存活信号，但不足以引起肺细胞死亡。结论在急性，亚慢性和慢性水平下暴露于CS的大鼠肺可能代表吸烟者，其生存信号发生改变，但与肺细胞死亡无关，而肺气肿与肺细胞凋亡有关。

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