Department of Respiratory Medicine, University of Leipzig, Leipzig, Germany.
Respirology. 2010 Feb;15(2):343-8. doi: 10.1111/j.1440-1843.2009.01701.x.
Vascular endothelial growth factor (VEGF) has protective as well as injurious effects in ARDS/acute lung injury. The influence of VEGF was investigated in a model of stretch-induced apoptosis. High-amplitude mechanical stretch induced the secretion of VEGF. High VEGF concentrations may prevent stretch-induced apoptosis by restoring stretch-impaired phospatidylinositol-3 kinase signalling.
Vascular endothelial growth factor (VEGF) is strongly expressed in the alveolar epithelium. VEGF has been shown to exhibit protective as well as injurious effects in ARDS/acute lung injury. We therefore investigated the influence of VEGF in a model of stretch-induced apoptosis.
Isolated rat alveolar type II (ATII) cells were subjected to high-amplitude cyclic mechanical stretch (40 per minute, 30% change in surface area) for 24 h. VEGF gene expression was investigated by real-time reverse transcription-PCR. Concentrations of VEGF in culture supernatants of stretched cells were determined by ELISA. Apoptosis of cells following stretching was assessed by flow cytometry.
Vascular endothelial growth factor gene expression increased during the first 4 h of stretching and then declined to a similar level to that of static control cells. VEGF concentrations in cell supernatants increased in response to mechanical stretch, as compared with those in supernatants of static control cells. Incubation of ATII cells with higher concentrations of VEGF (50 ng/mL) during stretching inhibited apoptosis, presumably by restoring stretch-impaired phosphatidylinositol-3 kinase signalling. However, blocking free VEGF in the supernatant with an anti-VEGF antibody did not influence stretch-induced apoptosis.
These findings suggest that high-amplitude mechanical stretch induced secretion of VEGF, which in high concentrations, may prevent stretch-induced apoptosis. In this model, however, the protective influence of VEGF was not essential for survival of ATII cells subjected to high-amplitude mechanical stretch.
血管内皮生长因子（VEGF）在急性呼吸窘迫综合征/急性肺损伤中既有保护作用，也有损伤作用。本研究旨在探讨 VEGF 在牵张诱导的细胞凋亡模型中的作用。高振幅机械牵张可诱导 VEGF 的分泌。高浓度的 VEGF 可能通过恢复牵张损伤的磷酸肌醇 3 激酶信号转导来预防牵张诱导的细胞凋亡。
血管内皮生长因子（VEGF）在肺泡上皮细胞中强烈表达。在急性呼吸窘迫综合征/急性肺损伤中，VEGF 表现出保护和损伤作用。因此，我们研究了 VEGF 在牵张诱导的细胞凋亡模型中的作用。
分离的大鼠肺泡Ⅱ型（ATII）细胞接受高振幅循环机械牵张（40 次/分钟，表面积变化 30%）24 小时。采用实时逆转录聚合酶链反应（PCR）检测 VEGF 基因表达。ELISA 法检测牵张细胞培养上清液中 VEGF 的浓度。通过流式细胞术评估细胞牵张后的凋亡情况。
VEGF 基因表达在牵张的前 4 小时增加，然后下降到与静态对照细胞相似的水平。与静态对照细胞相比，机械牵张后细胞上清液中的 VEGF 浓度增加。在牵张过程中，与较高浓度的 VEGF（50ng/ml）孵育可抑制细胞凋亡，推测是通过恢复牵张损伤的磷酸肌醇 3 激酶信号转导。然而，用抗 VEGF 抗体阻断上清液中的游离 VEGF 并不影响牵张诱导的细胞凋亡。
这些发现表明，高振幅机械牵张诱导 VEGF 的分泌，高浓度的 VEGF 可能预防牵张诱导的细胞凋亡。然而，在该模型中，VEGF 的保护作用对于高振幅机械牵张的 ATII 细胞的存活并不是必需的。
