Genome‑wide analysis of DNA methylation in rat lungs with lipopolysaccharide‑induced acute lung injury

Zhang,Xiao‑Qiang; Lv,Chang‑Jun; Liu,Xiang‑Yong; Hao,Dong; Qin,Jing; Tian,Huan‑Huan; Li,Yan; Wang,Xiao‑Zhi

doi:10.3892/mmr.2013.1405

Genome‑wide analysis of DNA methylation in rat lungs with lipopolysaccharide‑induced acute lung injury

Authors:
- Xiao‑Qiang Zhang
- Chang‑Jun Lv
- Xiang‑Yong Liu
- Dong Hao
- Jing Qin
- Huan‑Huan Tian
- Yan Li
- Xiao‑Zhi Wang
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Affiliations: Department of Respiratory and Intensive Care Unit, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, P.R. China, Department of Respiratory and Intensive Care Unit, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, P.R. China, Department of Cell Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
Published online on: March 28, 2013 https://doi.org/10.3892/mmr.2013.1405
Pages: 1417-1424

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Abstract

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are associated with high morbidity and mortality in patients, however, the precise pathogenesis of ALI/ARDS remains unknown. Lipopolysaccharide (LPS) exhibits a number of critical functions and may be associated with the DNA methylation of genes in the lungs. In the present study a genome‑wide analysis of DNA methylation was performed in rat lungs with LPS‑induced ALI/ARDS. Normal and LPS‑induced lung tissues with ALI were analyzed using methylated DNA immunoprecipitation and a rat DNA methylation promoter plus CpG island microarray and the candidate genes were validated by quantitative reverse transcriptase polymerase chain reaction (qRT‑PCR). Aberrant DNA methylation of the promoter regions of 1,721 genes and the CpG islands of 990 genes was identified when normal lung tissues and lung tissues with LPS‑induced ALI/ARDS were compared. These genes were commonly located on chromosomes 1, 3, 5, 7 and 10 (P<0.01). Methylation level and CpG density were compared and it was found that genes associated with high CpG density promoters had a high ratio of methylation. Furthermore, we performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In addition, three genes (Mapk3, Pak1 and Rac2) were validated in the control and lung tissues with ALI by RT‑PCR. The results indicate that aberrant DNA methylation of lung tissues may be involved in the pathophysiology of LPS‑induced ALI/ARDS. Future studies are required to evaluate the therapeutic and prognostic value of the current novel observations in ALI/ARDS.

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