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) All Versions of this Article: 32/1/128    most recent 00108.2007v1 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 Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Boucherat, O. Articles by Bourbon, J. R. Search for Related Content PubMed PubMed Citation Articles by Boucherat, O. Articles by Bourbon, J. R.

Gene expression profiling in lung fibroblasts reveals new players in alveolarization

¹ Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 841, Institut Mondor de Recherche Biomédicale (IMRB), Département de Biologie et Thérapeutiques Cardiorespiratoires et Hépatiques
² IFR10, Faculté de Médecine, Université Paris 12, Créteil
³ Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch
⁴ IFR10, Plate-forme de Génomique, INSERM, Hôpital Henri Mondor, Créteil, France

Little is known about the molecular basis of lung alveolarization. We used a microarray profiling strategy to identify novel genes that may regulate the secondary septation process. Rat lung fibroblasts were extemporaneously isolated on postnatal days 2, 7, and 21, i.e., before, during, and after septation, respectively. Total RNA was extracted, and cRNAs were hybridized to Affymetrix rat genome 230 2.0 microarrays. Expression levels of a selection of genes were confirmed by real-time PCR. In addition to genes already known to be upregulated during alveolarization including drebrin, midkine, Fgfr3, and Fgfr4, the study allowed us to identify two remarkable groups of genes with opposite profiles, i.e., gathering genes either transiently up- or downregulated on day 7. The former group includes the transcription factors retinoic acid receptor (RXR)- and homeobox (Hox) a2, a4, and a5 and genes involved in Wnt signaling (Wnt5a, Fzd1, and Ndp); the latter group includes the extracellular matrix components Comp and Opn and the signal molecule Slfn4. Profiling in whole lung from fetal life to adulthood confirmed that changes were specific for alveolarization. Two treatments that arrest septation, hyperoxia and dexamethasone, inhibited the expression of genes that are upregulated during alveolarization and conversely enhanced that of genes weakly expressed during alveolarization and upregulated thereafter. The possible roles of these genes in secondary septation are discussed. Gene expression profiling analysis on freshly isolated cells represents a powerful approach to provide new information about differential regulation of genes during alveolarization and pathways potentially involved in the pathogenesis of bronchopulmonary dysplasia.

bronchopulmonary dysplasia; hyperoxia; Hox; Wnt; Opn