Chronic Hypoxia and Rat Lung Development: Analysis by Morphometry and Directed Microarray

Abstract

It is unclear how sublethal hypoxia affects lung development. To investigate the effects of chronic hypoxia on postnatal lung remodeling, we treated neonatal rats with FIO 2 of 0.12 for 10 d and analyzed lung development by morphometry and gene expression by DNA microarray. Our results showed the neonatal rats exposed to hypoxia reduced body weight by 42% and wet lung weight by 32% compared with the neonatal rats exposed to normoxia. In the neonatal rats exposed to hypoxia, the radial alveolar counts were decreased to 5.6 from 7.9 and the mean linear intercepts were increased to 56.5 m from 38.2 m. In DNA microarray analysis, approximately half of probed genes were unknown. Chronic hypoxia significantly regulated expression of genes that are involved in pathogenesis of pulmonary hypertension and postnatal lung remodeling. Chemokine ligand 12, jagged 2 were among those upregulated; c-kit, ephrin A1, and Hif-2␣ were among those downregulated. The altered expression of those genes was correlated with the lung development and remodeling. (Pediatr Res 64: 56-62, 2008)

Transcriptome profiling of the newborn mouse lung after hypoxia and reoxygenation: hyperoxic reoxygenation affects mTOR signaling pathway, DNA repair, and JNK-pathway regulation

“…In the four groups following hypoxia (H21, H40, H60, and H100) as compared with controls (C21), 761 out of the 34,760 probes on the microarray chip were found to be significantly differentially expressed in whole-lung homogenates using the automatic thresholding rule by Bayesian ANOVA of microarrays (BAMarray) (18). Among the 24,674 probe sets with known gene symbol, 564 genes were significantly differentially expressed.…”

“…Models of chronic hypoxia (18) or hyperoxia (13) demonstrate altered pulmonary morphology and gene expression patterns. In this study, our aim was to investigate the transcriptional changes from 120 min of hypoxia followed by reoxygenation with graded FiO 2 supplemental oxygen, resembling resuscitation of an asphyxiated slightly preterm baby.…”

Expression profiling analysis of hypoxic pulmonary disease

“…DNA microarray technology is a powerful tool for rapid, comprehensive, and quantitative analysis of gene expression profiles of normal and disease states (Chen et al, 2001). This technology has been successfully applied to identify potential target genes for pulmonary hypoxia (Truog et al, 2008;Zhou et al, 2011). In this study, we aimed to apply the same approach to compare gene responses to hypoxia for different hypoxia exposure time in human pulmonary microvascular endothelial cells.…”

Life-long consequences of postnatal normoxia exposure in rats raised at high altitude

“…It is well documented that postnatal hypoxia blunts growth (16) and induces several alterations of the respiratory system in adults. In rats and mice, postnatal hypoxia results in a lung tissue with fewer but larger alveoli, reduced surface-exchange area, limitations of respiratory gas exchange, and signs of pulmonary hypertension (6,31,50). Similarly, adequate development of the respiratory control system is also dependent on postnatal oxygen level.…”