DNA microarray analysis of neonatal mouse lung connects regulation of KDR with dexamethasone-induced inhibition of alveolar formation
| Autor: | Eric P. Hoffman, Linda Biadasz Clerch, Alexander S. Baras, Gloria DeCarlo Massaro, Donald Massaro |
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| Rok vydání: | 2004 |
| Předmět: |
Pulmonary and Respiratory Medicine
Pulmonary Circulation medicine.medical_specialty Physiology Retinoic acid Neovascularization Physiologic Antineoplastic Agents Tretinoin Biology Dexamethasone Mice chemistry.chemical_compound Downregulation and upregulation Pregnancy Physiology (medical) Internal medicine polycyclic compounds medicine Animals Cluster Analysis Receptor Glucocorticoids Oligonucleotide Array Sequence Analysis Regulation of gene expression Microarray analysis techniques Kinase Gene Expression Regulation Developmental Kinase insert domain receptor Cell Biology Vascular Endothelial Growth Factor Receptor-2 Molecular biology Mice Inbred C57BL Pulmonary Alveoli Endocrinology Animals Newborn chemistry Female hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 286:L411-L419 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00306.2003 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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