Li-Da Chen1,2, Qin Chen3, Xue-Jun Lin4, Qing-Shi Chen1,5, Yu-Zhen Huang6, Run-Hua Wu3, Guo-Fu Lin1,7,8, Xiao-Yun Huang1,7,8, Qi-Chang Lin9,10,11. 1. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, People's Republic of China. 2. Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, People's Republic of China. 3. College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, People's Republic of China. 4. Department of Laboratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou,, Fujian Province, People's Republic of China. 5. The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, People's Republic of China. 6. Department of Pathology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, People's Republic of China. 7. Fujian Provincial Sleep-Disordered Breathing Clinic Center, Fuzhou, Fujian Province, People's Republic of China. 8. Laboratory of Respiratory Disease of the Fujian Medical University, Fuzhou, Fujian Province, People's Republic of China. 9. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, People's Republic of China. chang4e@126.com. 10. Fujian Provincial Sleep-Disordered Breathing Clinic Center, Fuzhou, Fujian Province, People's Republic of China. chang4e@126.com. 11. Laboratory of Respiratory Disease of the Fujian Medical University, Fuzhou, Fujian Province, People's Republic of China. chang4e@126.com.
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.
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.