HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplementary Material All Versions of this Article: 286/2/L411    most recent 00306.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (23) Citing Articles via Google Scholar Google Scholar Articles by Clerch, L. B. Articles by Massaro, D. Search for Related Content PubMed PubMed Citation Articles by Clerch, L. B. Articles by Massaro, D.

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

Lung Biology Laboratory, Departments of ¹Pediatrics, ²Biology, and ⁴Medicine, Georgetown University School of Medicine, Washington 20057; and ³Center 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

This article has been cited by other articles:

				S. V. Stinchcombe and M. Maden Retinoic Acid Induced Alveolar Regeneration: Critical Differences in Strain Sensitivity Am. J. Respir. Cell Mol. Biol., February 1, 2008; 38(2): 185 - 191. [Abstract] [Full Text] [PDF]

				O. Boucherat, M.-L. Franco-Montoya, C. Thibault, R. Incitti, B. Chailley-Heu, C. Delacourt, and J. R. Bourbon Gene expression profiling in lung fibroblasts reveals new players in alveolarization Physiol Genomics, December 19, 2007; 32(1): 128 - 141. [Abstract] [Full Text] [PDF]

				R. D. Bland, L. M. Mokres, R. Ertsey, B. E. Jacobson, S. Jiang, M. Rabinovitch, L. Xu, E. S. Shinwell, F. Zhang, and M. A. Beasley Mechanical ventilation with 40% oxygen reduces pulmonary expression of genes that regulate lung development and impairs alveolar septation in newborn mice Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1099 - L1110. [Abstract] [Full Text] [PDF]

				M. B. Yaylaoglu, B. M. Agbemafle, T. J. Oesterreicher, M. J. Finegold, C. Thaller, and S. J. Henning Diverse patterns of cell-specific gene expression in response to glucocorticoid in the developing small intestine Am J Physiol Gastrointest Liver Physiol, December 1, 2006; 291(6): G1041 - G1050. [Abstract] [Full Text] [PDF]

				K. C. Wade, S. H. Guttentag, L. W. Gonzales, K. L. Maschhoff, J. Gonzales, V. Kolla, S. Singhal, and P. L. Ballard Gene Induction during Differentiation of Human Pulmonary Type II Cells In Vitro Am. J. Respir. Cell Mol. Biol., June 1, 2006; 34(6): 727 - 737. [Abstract] [Full Text] [PDF]

				N. F. Voelkel, R. W. Vandivier, and R. M. Tuder Vascular endothelial growth factor in the lung Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L209 - L221. [Abstract] [Full Text] [PDF]

				B. M. Agbemafle, T. J. Oesterreicher, C. A. Shaw, and S. J. Henning Immediate early genes of glucocorticoid action on the developing intestine Am J Physiol Gastrointest Liver Physiol, May 1, 2005; 288(5): G897 - G906. [Abstract] [Full Text] [PDF]

				D. Massaro, G. D. Massaro, and L. B. Clerch Noninvasive delivery of small inhibitory RNA and other reagents to pulmonary alveoli in mice Am J Physiol Lung Cell Mol Physiol, November 1, 2004; 287(5): L1066 - L1070. [Abstract] [Full Text] [PDF]

				D. Massaro and G. D. Massaro Critical period for alveologenesis and early determinants of adult pulmonary disease Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L715 - L717. [Full Text] [PDF]