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RNA-seq-based transcriptome profiling reveals differential gene expression in the lungs of Sprague–Dawley rats during early-phase acute hypobaric hypoxia

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Abstract

Individuals subjected to hypobaric hypoxia at high altitudes may exhibit differential physiological responses in terms of susceptibility and tolerance to the development of hypoxia-related disorders. We studied early-phase gene expression in the lungs of Sprague–Dawley rats exhibiting such differential physiological responses after exposure to acute hypobaric hypoxia for 1 h at a simulated altitude of 9144 m. RNA-seq transcriptome profiling of lung tissues revealed differential gene expression in tolerant and susceptible groups, subsequently validated by qRT-PCR for ten selected differentially expressed genes. The gene expression pattern indicated hypometabolism and negative regulation of vasoconstriction in all groups except susceptible rats, coupled with altered MAPK, p53 and JAK-STAT signaling. Upregulation of early-phase response genes including Dusp1 (dual specificity phosphatase), Cdkn1a (cyclin-dependent kinase inhibitor 1A), Txnip (thioredoxin-interacting protein), Rgs1 (regulator of G-protein signaling 1) and Rgs2 (regulator of G-protein signaling 2) in susceptible rats indicated a progression toward growth arrest and apoptosis. Enhanced expression of cell adhesion molecules, wound healing and repair bioprocesses was observed in tolerant males. Upregulated Kcnj15 (potassium inwardly rectifying channel subfamily j membrane 15) and Vsig4 (V-set and Ig domain containing 4) variants in tolerant females suggested adaptation to hypoxia possibly by fluid reabsorption to avoid edematous conditions and suppression of T cell proliferation to avoid acute lung inflammation. Our study might help in understanding the molecular–physiological mechanisms associated with progressive damage in the lung tissues of susceptible and tissue-protective measures in tolerant rats during acute hypobaric hypoxia.

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Acknowledgments

The authors express their sincere thanks to the Director, DIPAS, DRDO, for providing financial support and animal house facilities for carrying out this work. We are also thankful to Dr. Saurabh Raghuvanshi, University of South Campus, New Delhi, for providing CLC Genomics Workbench facility. Our thanks are due to Mr. Bhagwat Singh and Mr. Deependra Pratap Singh for their technical support in animal handling and tissue collection.

Conflict of interest

The authors report no conflicts of interest and are alone responsible for the content and writing of the paper.

Ethical approval

The guidelines followed for the care and use of animals including the rearing conditions and all the procedures performed were approved by the Institute’s Animal Ethical Committee, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organisation, Delhi, India, and were in compliance with all the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India.

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  1. University School of Biotechnology (USBT), Guru Gobind Singh Indraprastha University, Sector 16C, Dwarka, New Delhi, 110078, India

    Priyanka Sharma & Prakash Chand Sharma

  2. Experimental Biology Division, Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organisation (DRDO), Timarpur, Lucknow Road, New Delhi, India

    Anju Bansal

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  1. Priyanka Sharma
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Correspondence to Prakash Chand Sharma.

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Communicated by S. Hohmann.

Data submission

We have deposited RNA-seq raw data and processed files of this experimental work in the GEO database repository of NCBI with series accession number GSE62688 and SRA study number SRP049242.

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Sharma, P., Bansal, A. & Sharma, P.C. RNA-seq-based transcriptome profiling reveals differential gene expression in the lungs of Sprague–Dawley rats during early-phase acute hypobaric hypoxia. Mol Genet Genomics 290, 2225–2240 (2015). https://doi.org/10.1007/s00438-015-1064-0

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