de Laplanche Elodie, Boudria Asma, Dacheux Estelle, Vincent Anne, Gadot Nicolas, Assade Fouzia, Le Corf Katy, Leroy Xavier, Mège Lechevallier Florence, Eymin Béatrice, Dalla Venezia Nicole, Simonnet Hélène
Université de Lyon, Lyon, F-69000, France Université Lyon 1, Lyon, F-69000, France Inserm U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, F-69000, France CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, F-69000, France.
Institut Albert Bonniot Equipe 2 Bases Moléculaires de la Progression des Cancers du Poumon, INSERM U823/Université Joseph Fourier, Grenoble, F-38000, France.
Physiol Rep. 2015 Jan 19;3(1). doi: 10.14814/phy2.12253. Print 2015 Jan 1.
As glucose is a mandatory nutrient for cell proliferation and renewal, it is suspected that glucose microenvironment is sensed by all cell types to regulate angiogenesis. Several glucose-sensing components have been partially described to respond to high glucose levels. However, little is known about the response to low glucose. Here, we used well-differentiated isolated normal rat renal tubules under normal oxygenation conditions to assess the angiogenic response to low glucose. In apparent paradox, but confirming observations made separately in other models, high glucose but also low glucose increased mRNA level of vascular endothelial growth factor A (VEGFA). A subset of mRNAs including hypoxia-inducible factor 1A (HIF1A), angiopoietin receptor (TIE-2), and VEGF receptor 2 (FLK1) were similarly glucose-sensitive and responded to low glucose by increased stability independently of HIF1A and HIF2A proteins. These results contribute to gain some insights as to how normal cells response to low glucose may play a role in the tumor microenvironment.
由于葡萄糖是细胞增殖和更新的必需营养素，因此有人怀疑所有细胞类型都能感知葡萄糖微环境以调节血管生成。已经部分描述了几种葡萄糖传感成分对高葡萄糖水平的反应。然而，对于低葡萄糖的反应却知之甚少。在这里，我们使用在正常氧合条件下分化良好的分离正常大鼠肾小管来评估对低葡萄糖的血管生成反应。明显矛盾的是，但与在其他模型中分别进行的观察结果一致，高葡萄糖以及低葡萄糖都会增加血管内皮生长因子A（VEGFA）的mRNA水平。包括缺氧诱导因子1A（HIF1A）、血管生成素受体（TIE-2）和VEGF受体2（FLK1）在内的一部分mRNA同样对葡萄糖敏感，并通过增加稳定性独立于HIF1A和HIF2A蛋白对低葡萄糖作出反应。这些结果有助于深入了解正常细胞对低葡萄糖的反应如何在肿瘤微环境中发挥作用。
