Title: Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice
Authors: Compernolle, Veerle ×
Brusselmans, Koen
Acker, Till
Hoet, Peter
Tjwa, Marc
Beck, Heike
Plaisance, Stéphane
Dor, Yuval
Keshet, Eli
Lupu, Florea
Nemery, Benoit
Dewerchin, Mieke
Van Veldhoven, Paul P
Plate, Karl
Moons, Lieve
Collen, Desire
Carmeliet, Peter #
Issue Date: Jul-2002
Publisher: Nature Pub. Co.
Series Title: Nature medicine vol:8 issue:7 pages:702-10
Abstract: Respiratory distress syndrome (RDS) due to insufficient production of surfactant is a common and severe complication of preterm delivery. Here, we report that loss of the hypoxia-inducible transcription factor-2alpha (HIF-2alpha) caused fatal RDS in neonatal mice due to insufficient surfactant production by alveolar type 2 cells. VEGF, a target of HIF-2alpha, regulates fetal lung maturation: because VEGF levels in alveolar cells were reduced in HIF-2alpha-deficient fetuses; mice with a deficiency of the VEGF(164) and VEGF(188) isoforms or of the HIF-binding site in the VEGF promotor died of RDS; intrauterine delivery of anti-VEGF-receptor-2 antibodies caused RDS and VEGF stimulated production of surfactant proteins by cultured type 2 pneumocytes. Intrauterine delivery or postnatal intratracheal instillation of VEGF stimulated conversion of glycogen to surfactant and protected preterm mice against RDS. The pneumotrophic effect of VEGF may have therapeutic potential for lung maturation in preterm infants.
ISSN: 1078-8956
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Pharmacology Section (-)
Molecular and Vascular Biology
Environment and Health - miscellaneous
Animal Physiology and Neurobiology Section - miscellaneous
Laboratory of Lipid Biochemistry and Protein Interactions
Occupational, Environmental and Insurance Medicine (-)
Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
× corresponding author
# (joint) last author

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