GSE62688
Transcriptome profiling based study of early gene responses in susceptible and tolerant rat lung tissues during acute hypobaric hypoxia
Aim: Acute hypobaric hypoxia occurs during fast ascent and brief sojourns to high altitudes. We aimed to elucidate early phase molecular mechanisms during hypobaric hypoxia that may contribute towards differential physiological responses in susceptible and tolerant rats. Methods: Sprague-Dawley rats representing susceptible, normal (moderate) and tolerant male and female groups were subjected to simulated acute hypobaric hypoxia for one hour at 9144 m and 24°C. The lung tissue samples were subjected to high throughput mRNA-seq based transcriptome profiling. Differential gene expression of selected genes was validated by qRT-PCR. Results: The cellular mechanisms found to be playing significant role in hypobaric hypoxia included MAPK, p53 and JAK-STAT signaling, and hypometabolism. Upregulated expression of early response genes including Dusp1, Cdkn1a, Txnip, Rgs1 and Rgs2 in susceptible rats indicated a progression towards growth arrest and apoptosis, while elevated expression of cell adhesion molecules, wound healing and repair bioprocesses was found in tolerant males. Upregulated Kcnj15 and Vsig4 variants in tolerant females suggested hypoxia adaptation by fluid reabsorption to avoid edematous conditions and suppression of T cell proliferation to avoid acute lung inflammation. Conclusion: The differential gene expression patterns in different experimental sets elucidated the physiological mechanisms associated with progressive damage in the lung tissues of susceptible and normal (moderate) rats, and tissue protective measures in tolerant rats during acute hypobaric hypoxia. Overall design: Transcriptome sequencing of 5 Sprague Dawley rat lung samples including 1 sample of normoxia as reference using Genome Analyser IIx