BACKGROUND: Fetal lung development requires proper coordination between lung epithelial and vascular morphogenesis. A major determinant in lung vascular development is vascular endothelial growth factor (VEGF), which is regulated by hypoxia-inducible factors (HIFs). VEGF is expressed in the airway epithelium, while its receptors (VEGFRs) are expressed in the pulmonary mesenchyme. The hypoxic environment in utero is beneficial for fetal organogenesis, especially vascular development. However, little is known about the expression of HIFs and VEGFR-2 in the human fetal lung in vitro. OBJECTIVES: The purpose of this study was to investigate the effects of hypoxia on fetal lung morphology and mRNA expression of VEGF, VEGFR-2, HIF-2alpha, and HIF-3alpha. METHODS: An explant culture technique was used to study the effects of normoxic and hypoxic conditions on human fetal lung. RESULTS: The morphology remained largely unchanged in explants cultured under hypoxic or normoxic conditions. Quantitative RT-PCR showed that the mRNA expression of VEGF-A, but not VEGFR-2 is upregulated in explants cultured at 1.5% compared with 21% oxygen. We observed a nonsignificant increase in HIF-2alpha and HIF-3alpha mRNA expression in explants cultured at 1.5% oxygen. These data suggest that the mRNA expression of VEGF, and possibly HIF-2alpha and HIF-3alpha, is regulated by hypoxia in the developing human lung. CONCLUSION: This lung explant culture model appears to be a valuable model to unravel the molecular mechanisms of human lung development. Copyright 2009 S. Karger AG, Basel.
BACKGROUND: Fetal lung development requires proper coordination between lung epithelial and vascular morphogenesis. A major determinant in lung vascular development is vascular endothelial growth factor (VEGF), which is regulated by hypoxia-inducible factors (HIFs). VEGF is expressed in the airway epithelium, while its receptors (VEGFRs) are expressed in the pulmonary mesenchyme. The hypoxic environment in utero is beneficial for fetal organogenesis, especially vascular development. However, little is known about the expression of HIFs and VEGFR-2 in the human fetal lung in vitro. OBJECTIVES: The purpose of this study was to investigate the effects of hypoxia on fetal lung morphology and mRNA expression of VEGF, VEGFR-2, HIF-2alpha, and HIF-3alpha. METHODS: An explant culture technique was used to study the effects of normoxic and hypoxic conditions on human fetal lung. RESULTS: The morphology remained largely unchanged in explants cultured under hypoxic or normoxic conditions. Quantitative RT-PCR showed that the mRNA expression of VEGF-A, but not VEGFR-2 is upregulated in explants cultured at 1.5% compared with 21% oxygen. We observed a nonsignificant increase in HIF-2alpha and HIF-3alpha mRNA expression in explants cultured at 1.5% oxygen. These data suggest that the mRNA expression of VEGF, and possibly HIF-2alpha and HIF-3alpha, is regulated by hypoxia in the developing human lung. CONCLUSION: This lung explant culture model appears to be a valuable model to unravel the molecular mechanisms of human lung development. Copyright 2009 S. Karger AG, Basel.
Authors: Marko Z Nikolić; Oriol Caritg; Quitz Jeng; Jo-Anne Johnson; Dawei Sun; Kate J Howell; Jane L Brady; Usua Laresgoiti; George Allen; Richard Butler; Matthias Zilbauer; Adam Giangreco; Emma L Rawlins Journal: Elife Date: 2017-06-30 Impact factor: 8.140
Authors: Daphne P de Wijs-Meijler; Dirk J Duncker; Dick Tibboel; Ralph T Schermuly; Norbert Weissmann; Daphne Merkus; Irwin K M Reiss Journal: Pulm Circ Date: 2017-01-01 Impact factor: 3.017
Authors: Marko Z Nikolić; Eva M Garrido-Martin; Flavia R Greiffo; Aurélie Fabre; Irene H Heijink; Agnes Boots; Catherine M Greene; Pieter S Hiemstra; Sabine Bartel Journal: ERJ Open Res Date: 2019-05-10