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Gene expression profiling in lung fibroblasts reveals new players in alveolarization.

Authors: Boucherat, O  Franco-Montoya, ML  Thibault, C  Incitti, R  Chailley-Heu, B  Delacourt, C  Bourbon, JR 
Citation: Boucherat O, etal., Physiol Genomics. 2007 Dec 19;32(1):128-41. Epub 2007 Oct 2.
Pubmed: (View Article at PubMed) PMID:17911382
DOI: Full-text: DOI:10.1152/physiolgenomics.00108.2007

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)-gamma 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.

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CRRD Object Information
CRRD ID: 2304247
Created: 2009-03-11
Species: All species
Last Modified: 2009-03-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.