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Effect of chronic intermittent hypoxia on gene expression profiles of rat liver: a better understanding of OSA-related liver disease

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Abstract

Purpose

Obstructive sleep apnea (OSA) and OSA-associated chronic intermittent hypoxia (CIH) have been suggested to be associated with increased risk of liver disease. Little is known about the biological pathophysiology and underlying molecular mechanisms. Here we use whole-genome expression profiling to explore the transcriptomic changes induced by CIH in rat liver.

Methods

Rats (n = 3) were exposed to CIH for 8 weeks and were compared with rats exposed to normoxia (n = 3). Illumina HiSeq 4000 platform was used to examine differentially expressed genes (DEGs) in the liver between control group and CIH rat model. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate DEGs. Biological functions of DEGs were determined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.

Results

Compared with control group, 318 genes were identified to be dysregulated in the liver of CIH rat model, with 211genes upregulated and 107 genes downregulated. Bioinformatics analysis showed that these genes were extensively related to various physiologic processes such as hepatic metabolism, apoptotic process, and oxidative stress. 10 genes with 5 upregulated and 5 downregulated were selected and further verified by qRT-PCR.

Conclusions

CIH resulted in altered gene expression patterns in the liver of rat. The DEGs were related to various physiological and pathological processes in CIH rat liver. These data provide a better understanding of the mechanisms and underlying molecular changes of OSA-related liver disease.

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Funding

This work was supported by National Natural Science Foundation of China (81870074), National Natural Science Foundation of China (81900088), and Startup Fund for Scientific Research from Fujian Medical University (2017XQ1117).

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Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China

    Li-Da Chen, Qing-Shi Chen, Guo-Fu Lin, Xiao-Yun Huang & Qi-Chang Lin

  2. Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, People’s Republic of China

    Li-Da Chen

  3. College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, People’s Republic of China

    Qin Chen & Run-Hua Wu

  4. Department of Laboratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou,, Fujian Province, People’s Republic of China

    Xue-Jun Lin

  5. The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, People’s Republic of China

    Qing-Shi Chen

  6. Department of Pathology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, People’s Republic of China

    Yu-Zhen Huang

  7. Fujian Provincial Sleep-Disordered Breathing Clinic Center, Fuzhou, Fujian Province, People’s Republic of China

    Guo-Fu Lin, Xiao-Yun Huang & Qi-Chang Lin

  8. Laboratory of Respiratory Disease of the Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China

    Guo-Fu Lin, Xiao-Yun Huang & Qi-Chang Lin

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  1. Li-Da Chen
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  2. Qin Chen
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Corresponding author

Correspondence to Qi-Chang Lin.

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The authors declare that they have no conflict of interest.

Ethics statement

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Comment

A study trying to find elements of response about how obstructive sleep apnea can damage certain organs, here through repetitive oxygen desaturations on the liver capable of genes expression alteration.

Philippe Bordier

France

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Chen, LD., Chen, Q., Lin, XJ. et al. Effect of chronic intermittent hypoxia on gene expression profiles of rat liver: a better understanding of OSA-related liver disease. Sleep Breath 24, 761–770 (2020). https://doi.org/10.1007/s11325-019-01987-0

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  • DOI: https://doi.org/10.1007/s11325-019-01987-0

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