Gene expression profiling in lung fibroblasts reveals new players in alveolarization

Olivier Boucherat, Marie Laure Franco-Montoya, Christelle Thibault, Roberto Incitti, Bernadette Chailley-Heu, Christophe Delacourt, Jacques R. Bourbon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

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 down-regulated on day 7. The former group includes the transcription factors retinoic acid receptor (RXR)-γ 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.

Original languageEnglish (US)
Pages (from-to)128-141
Number of pages14
JournalPhysiological Genomics
Volume32
Issue number1
DOIs
StatePublished - Dec 19 2007

Keywords

  • Bronchopulmonary dysplasia
  • Hox
  • Hyperoxia
  • Opn
  • Wnt

ASJC Scopus subject areas

  • Physiology
  • Genetics

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