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, St├ęphane
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:Occupational, Environmental and Insurance Medicine (-)
Environment and Health - miscellaneous
Laboratory of Lipid Biochemistry and Protein Interactions
Animal Physiology and Neurobiology Section - miscellaneous
Pharmacology Section (-)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
Vesalius Research Centre (-)
Molecular and Vascular Biology
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
Compernolle et al._2002_Nature Med_vol8_p702-710.pdf Published 1572KbAdobe PDFView/Open Request a copy

These files are only available to some KU Leuven Association staff members


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science