Gene expression profiling in lung fibroblasts reveals new players in alveolarization
| Autor: | Roberto Incitti, Marie-Laure Franco-Montoya, Olivier Boucherat, Christophe Delacourt, Christelle Thibault, Jacques R. Bourbon, Bernadette Chailley-Heu |
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| Rok vydání: | 2007 |
| Předmět: |
Physiology
Biology Bioinformatics Dexamethasone Novel gene Pregnancy Genetics medicine Animals Hox gene Lung Oligonucleotide Array Sequence Analysis Homeodomain Proteins Hyperoxia Regulation of gene expression Gene Expression Profiling Wnt signaling pathway Rats Cell biology Pulmonary Alveoli Gene expression profiling medicine.anatomical_structure Animals Newborn Gene Expression Regulation Female medicine.symptom Microarray profiling |
| Zdroj: | Physiological Genomics. 32:128-141 |
| ISSN: | 1531-2267 1094-8341 |
| DOI: | 10.1152/physiolgenomics.00108.2007 |
| Popis: | 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)-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. |
| Databáze: | OpenAIRE |
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