Vascular endothelial growth factor promotes physical wound repair and is anti-apoptotic in primary distal lung epithelial and A549 cells

Abstract

In addition to its known effects on endothelial cells, VEGF acts as a growth and anti-apoptotic factor on alveolar epithelial cells. VEGF treatment may have potential as a rescue therapy for diseases associated with alveolar epithelial damage such as acute respiratory distress syndrome.

A Role for Forkhead Box A1 in Acute Lung Injury

“…AT-2 cells were stimulated with hydrogen peroxide (H 2 O 2 , 0.5 mM, Xilong Chemical Factory, China). A dose of H 2 O 2 was chosen that was consistent with previous reports [28,29] and with our pilot study, in which we found that a lower dose (0.25 mM) of H 2 O 2 did not induce obvious AT-2 cells injury. At 0, 1, 2, 4, 8, 16, 24 h after treatment, cells were harvested and mRNA and protein was extracted to determine FoxA1 expression.…”

Pulmonary Epithelial Neuropilin-1 Deletion Enhances Development of Cigarette Smoke–induced Emphysema

“…VEGF has autocrine effects on growth and proliferation of pulmonary epithelial cells in vitro and may protect against oxidant-induced apoptosis of cultured primary lung epithelial cells and epithelial-derived cell lines (38,60). Moreover, VEGF stimulates branching morphogenesis of renal tubular epithelium in culture (61).…”

“…Because VEGF, a Nrp1 ligand, promotes cell survival (38,59) and acts as a mitogen for both epithelial (60-62) and endothelial (63) cells, we measured the concentration of VEGF in both lung lavage and tissue lysates. As indicated in Figure 6 (top panel), levels of VEGF in lung lavage fluid did not differ significantly between conditionally Nrp1-deficient mice and littermates maintained in FA.…”

Gene regulation in the adaptive process to hypoxia in lung epithelial cells

“…In the alveolar epithelium, VEGF was localized at the luminal surface of alveolar walls, mostly in alveolar epithelial type II cells (57). In vitro, A549 cells as well as primary rat alveolar epithelial cells express VEGF transcripts and their receptors Flk-1 and Flt-1 (6,38,45). The transcripts correspond to the three major VEGF isoforms previously described: VEGF 121 and VEGF 165 that are secreted in a soluble form and VEGF 189 that remains cell surface associated or is primarily deposited in the extracellular matrix (6).…”

“…Second, VEGF may exert autocrine or paracrine regulatory roles through the functional VEGF receptors present on alveolar epithelial cells (8). Thus, in lung explants, VEGF modulates epithelial cell proliferation and surfactant protein expression, and, in A549 cells, VEGF promotes wound repair and is antiapoptotic (45). Finally, because VEGF receptor-1 (Flt-1) has been reported to be present on monocytes/macrophages, the activation of which leads to monocyte activation and chemotaxis (11), it could be hypothesized that apical secretion of VEGF may play a role in the recruitment of immune cells in the alveolar space.…”