Expression and regulation of vascular endothelial growth factor in human pulmonary epithelial cells

Abstract

Vascular endothelial growth factor (VEGF) is a potent endothelial cell growth and permeability factor highly expressed in rodent alveolar epithelium after injury and repair. To investigate VEGF synthesis in human lung epithelial cells, we examined VEGF expression by cultured cells under basal conditions and after cytokine treatment or oxidative stress. Basal VEGF expression was detected in transformed human epithelial cell lines (A549 and 1HAEo-) and in primary human bronchial epithelial cells with RT-PCR, Western blot, and immunocytochemistry. Among the cytokines tested, only transforming growth factor-beta1 increased the levels of excreted VEGF(165) as measured by ELISA. Under hypoxia (0% O(2) for 24 h), the VEGF(165) level increased fivefold, and this effect was O(2) concentration dependent. VEGF concentrations in the medium of all the cell types studied reached values similar to those found in bronchoalveolar lavage fluids from normal patients. Endothelial cells (human umbilical vein endothelial cells) exposed to conditioned medium from primary bronchial epithelial cell cultures showed an increased growth rate, which was inhibited in the presence of a specific neutralizing antibody to VEGF. These results suggest that lung epithelial cells participate in the endothelial repair and angiogenesis that follow lung injury through the synthesis of VEGF.

Hyperoxia enhances VEGF release from A549 cells via post-transcriptional processes

“…Similar findings have been reported in premature, non-human primates treated with oxygen and mechanical ventilation [32]. Transcripts corresponding to each of the major splice variants, VEGF 189 , VEGF 165 , and VEGF 121 , have been previously identified in A549 cells [33]. In the current study, exposure to hyperoxia failed to alter the expression of any isoforms over time or in comparison to cells grown in room air, demonstrating that alternate splicing cannot account for the increase in medium-derived VEGF.…”

Vascular endothelial growth factor mRNA and protein expression in airway epithelial cell linesin vitro

“…However, BOUSSAT et al [36] reported that primary human bronchial epithelial cells expressed VEGF and that the expression was upregulated by hypoxia and TGF-b1 treatment, as well as transformed human epithelial cells lines, including A549 cells [36]. The released VEGF from primary human bronchial epithelial cells was VEDF165 and had mitogenic activity of endothelial cells.…”

Anti-Vascular Endothelial Growth Factor Gene Therapy Attenuates Lung Injury and Fibrosis in Mice

“…In contrast to the VEGF levels in the plasma, those in the epithelial lining fluid changed in the opposite direction with recovery from injury (37). Kaner et al (38) suggested that alveolar epithelial cells are damaged in ARDS, possibly leading to the decreased levels of VEGF, because alveolar epithelial cells are the predominant source of VEGF (39). Accordingly, increased VEGF levels in the alveolar space may reflect recovery from ARDS (37).…”