DNA microarray analysis of neonatal mouse lung connects regulation of KDR with dexamethasone-induced inhibition of alveolar formation.
Treatment of newborn mice with dexamethasone (Dex) inhibits the subdivision of lung saccules to form alveoli; treatment with all-trans retinoic acid (RA) prevents this inhibition of septation. To better understand the early molecular signals responsible for the effects of Dex and RA, Affymetrix gene profiling was done on RNA isolated from 4-day-old mice after treatment with 1) diluent, 2) RA (1 mg/kg), 3) Dex (0.7 microg/pup), or 4) RA + Dex. Each sample was assayed in duplicate on U74Av2 GeneChips. Data were analyzed with Affymetrix suite 5.0, corrected for saturation, and evaluated with GeneSpring 5.1 software. Stringent filtering of data by the global error model and condition-to-condition comparisons was used to identify 46 genes demonstrating significantly different expression between the lungs of Dex- and RA + Dex-treated mice. A query of the gene ontology database revealed that the major biological processes affected by treatment with Dex and RA were cell growth/maintenance and cellular communication. On the basis of microarray data analysis, we hypothesize that Dex-induced inhibition of septation is associated with a block in angiogenesis due to downregulation of the kinase domain receptor (KDR), also known as VEGF receptor-2 and fetal liver kinase, and that the downregulation of KDR is prevented by treatment with RA.
Clerch
Linda Biadasz
LB
Department of Pediatrics, Georgetown University School of Medicine, 3900 Reservoir Rd., NW, Washington, DC 20057, USA. clerchlb@georgetown.edu
Baras
Alex S
AS
Massaro
Gloria DeCarlo
GD
Hoffman
Eric P
EP
Massaro
Donald
D
D000818:Animals; D000831:Animals, Newborn; D000970:Antineoplastic Agents / Q000494:pharmacology; D016000:Cluster Analysis; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
D000970:Antineoplastic Agents; D005938:Glucocorticoids; D014212:Tretinoin; D003907:Dexamethasone; D040301:Vascular Endothelial Growth Factor Receptor-2