Transcriptional Programs Controlling Perinatal Lung Maturation

作者：Yan Juan Xu, Yanhua Wang, Valérie Besnard, Machiko Ikegami, Susan E. Wert, Caleb S. Heffner, Stephen A. Murray, Leah Rae Donahue, Jeffrey A. Whitsett · 发表于：PLoS ONE · 年份：2012 · DOI：10.1371/journal.pone.0037046 · 被引用次数：82 · 研究领域：Neonatal Respiratory Health Research、Congenital Diaphragmatic Hernia Studies、Infant Nutrition and Health

The timing of lung maturation is controlled precisely by complex genetic and cellular programs.Lung immaturity following preterm birth frequently results in Respiratory Distress Syndrome (RDS) and Broncho-Pulmonary Dysplasia (BPD), which are leading causes of mortality and morbidity in preterm infants.Mechanisms synchronizing gestational length and lung maturation remain to be elucidated.In this study, we designed a genome-wide mRNA expression time-course study from E15.5 to Postnatal Day 0 (PN0) using lung RNAs from C57BL/6J (B6) and A/J mice that differ in gestational length by ,30 hr (B6,A/J).Comprehensive bioinformatics and functional genomics analyses were used to identify key regulators, bioprocesses and transcriptional networks controlling lung maturation.We identified both temporal and strain dependent gene expression patterns during lung maturation.For time dependent changes, cell adhesion, vasculature development, and lipid metabolism/transport were major bioprocesses induced during the saccular stage of lung development at E16.5-E17.5.CEBPA, PPARG, VEGFA, CAV1 and CDH1 were found to be key signaling and transcriptional regulators of these processes.Innate defense/immune responses were induced at later gestational ages (E18.5-20.5),STAT1, AP1, and EGFR being important regulators of these responses.Expression of RNAs associated with the cell cycle and chromatin assembly was repressed during prenatal lung maturation and was regulated by FOXM1, PLK1, chromobox, and hig...