Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A heparin-binding growth factor, midkine, is the product of a retinoic acid-responsive gene. Since retinol plays critical roles in lung development and treatment of bronchopulmonary dysplasia, and midkine has been implicated in the maturation of lung explants and in cytoprotection, we herein examined midkine expression during postnatal development of the lungs and hyperoxic lung injury. Midkine protein transiently increased to a maximum level at around 4 days postnatal. Immunohistochemistry revealed that the amounts of midkine increased in resident alveolar cells, but not in smooth muscle cells or the large airway epithelium. If neonatal mice were exposed to >95% oxygen, lung development was impaired and midkine expression was suppressed. In contrast, when adult mouse lungs as well as in vitro cultured lung adenocarcinoma cells were exposed to hyperoxia, midkine expression was not affected. Furthermore, a pronounced induction of midkine by retinoic acid was observed in neonatal lungs. The results indicate that midkine expression is associated with postnatal lung development, but not necessarily with hyperoxic cell damage.
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PMID:Midkine expression is associated with postnatal development of the lungs. 1220 52

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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PMID:Gene expression profiling in lung fibroblasts reveals new players in alveolarization. 1791 82