DNA microarray analysis of neonatal mouse lung connects regulation of KDR with dexamethasone-induced inhibition of alveolar formation

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 286; no. 2; pp. 411 - L419
• Main Authors: Clerch, Linda Biadasz, Baras, Alex S, Massaro, Gloria DeCarlo, Hoffman, Eric P, Massaro, Donald
• Format: Journal Article
• Language: English
• Published: United States 01.02.2004
• Subjects: Animals; Animals, Newborn; Antineoplastic Agents - pharmacology; Cluster Analysis; Dexamethasone - pharmacology; Female; Gene Expression Regulation, Developmental - drug effects; Glucocorticoids - pharmacology; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Oligonucleotide Array Sequence Analysis; Pregnancy; Pulmonary Alveoli - blood supply; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - physiology; Pulmonary Circulation - drug effects; Pulmonary Circulation - physiology; Tretinoin - pharmacology; Vascular Endothelial Growth Factor Receptor-2 - genetics
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00306.2003

Lung Biology Laboratory, Departments of 1 Pediatrics, 2 Biology, and 4 Medicine, Georgetown University School of Medicine, Washington 20057; and 3 Center for Genetic Medicine, Children's National Medical Center, Washington, District of Columbia 20010 Submitted 3 September 2003 ; accepted in final form 28 October 2003 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 µg/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. lung development; corticosteroid; retinoic acid; angiogenesis; kinase domain receptor Address for reprint requests and other correspondence: L. Biadasz Clerch, Lung Biology Lab., Georgetown Univ. School of Medicine, Preclinical Science Bldg., GM12, Box 571481, 3900 Reservoir Rd., NW, Washington, DC 20057 (E-mail: clerchlb{at}georgetown.edu ).