Genome‑wide analysis of DNA methylation in rat lungs with lipopolysaccharide‑induced acute lung injury.
Genome‑wide analysis of DNA methylation in rat lungs with lipopolysaccharide‑induced acute lung injury.
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DOI：
10.3892/mmr.2013.1405
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发表时间：
2013-05
影响因子：
3.4
通讯作者：
Xiao-qiang Zhang;Chang-jun Lv;Xiangyong Liu;Dong Hao;J. Qin;Huan-huan Tian;Yan Li;Xiao-zhi Wang
中科院分区：
文献类型：
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作者：
Xiao-qiang Zhang;Chang-jun Lv;Xiangyong Liu;Dong Hao;J. Qin;Huan-huan Tian;Yan Li;Xiao-zhi Wang
急性肺损伤（acute lung injury，ALI）和急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）的发病率和死亡率较高，但其确切的发病机制尚不清楚。脂多糖（LPS）具有许多重要功能，可能与肺中基因的DNA甲基化有关。在本研究中，对LPS诱导的ALI/ARDS大鼠肺进行了全基因组DNA甲基化分析。采用甲基化DNA免疫沉淀和大鼠DNA甲基化启动子加CpG岛微阵列分析正常和LPS诱导的ALI肺组织，并通过定量逆转录聚合酶链反应（qRT-PCR）验证候选基因。当比较正常肺组织和LPS诱导的ALI/ARDS肺组织时，确定了1，721个基因的启动子区域和990个基因的CpG岛的异常DNA甲基化。这些基因主要分布在1、3、5、7和10号染色体上（P<0.01）。比较甲基化水平和CpG密度，发现与高CpG密度启动子相关的基因具有高甲基化比率。此外，我们进行了基因本体论（GO）和京都基因和基因组百科全书（KEGG）的途径分析。此外，通过RT-PCR，在对照和ALI肺组织中验证了三个基因（Mapk 3，Pak 1和Rac 2）。结果表明，肺组织DNA甲基化异常可能参与了LPS诱导的ALI/ARDS的病理生理过程。未来的研究需要评估目前新的观察结果在ALI/ARDS中的治疗和预后价值。
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.