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首页> 外文期刊>American Journal of Physiology >Pleiotropic role of VEGF-A in regulating fetal pulmonary mesenchymal cell turnover.
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Pleiotropic role of VEGF-A in regulating fetal pulmonary mesenchymal cell turnover.

机译：VEGF-A在调节胎儿肺间充质细胞更新中的多效性作用。

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Tight regulation of VEGF-A production and signaling is important for the maintenance of lung development and homeostasis. VEGF null mice have provided little insight into the role of VEGF during the later stages of lung morphogenesis. Therefore, we examined the in vitro effects of autocrine and paracrine VEGF-A production and the inhibition of VEGF-A signaling on a Flk-1-negative subset of fetal pulmonary mesenchymal cells (pMC). We hypothesized that VEGF-A receptor signaling regulates turnover of fetal lung mesenchyme in a cell cycle-dependent manner. VEGF receptor blockade with SU-5416 caused cell spreading and decreased proliferation and bcl-2 localization. Nuclear expression of the cell cycle inhibitory protein, p21, was increased with SU-5416 treatment, and p27 was absent. Autocrine VEGF production by pMC resulted in proliferation and p21/p27-dependent contact inhibition. In contrast, exogenous VEGF-A increased cell progression through the cell cycle. Selective activation of Flt by placental growth factor demonstrated the importance of this receptor/kinase in the VEGF-A responsiveness of pMC. The expression and localization of the survival factor bcl-2 was dependent on VEGF. These results provide evidence that VEGF-A plays a critical role in the regulation of fetal pulmonary mesenchymal proliferation, survival, and the subsequent development of normal lung architecture through bcl-2 and p21/p27-dependent cell cycle control.
机译：严格调节VEGF-A的产生和信号传导对于维持肺部发育和体内平衡非常重要。 VEGF无效小鼠对肺形态发生后期阶段VEGF的作用了解甚少。因此，我们检查了自分泌和旁分泌VEGF-A产生的体外作用以及对胎儿肺间充质细胞（pMC）Flk-1阴性亚群的VEGF-A信号传导的抑制作用。我们假设VEGF-A受体信号传导以细胞周期依赖性方式调节胎儿肺间充质的转换。 SU-5416对VEGF受体的阻滞作用导致细胞扩散，增殖和bcl-2定位降低。 SU-5416处理可增加细胞周期抑制蛋白p21的核表达，而p27则不存在。 pMC产生的自分泌VEGF导致增殖和p21 / p27依赖性接触抑制。相反，外源性VEGF-A在整个细胞周期中增加了细胞进程。胎盘生长因子对Flt的选择性激活证明了该受体/激酶在pMC的VEGF-A反应性中的重要性。生存因子bcl-2的表达和定位取决于VEGF。这些结果提供了证据，表明VEGF-A通过bcl-2和p21 / p27依赖性细胞周期控制在胎儿肺间充质增殖，存活以及随后的正常肺结构发展中起着至关重要的作用。

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