Potential mechanism and key genes involved in mechanical ventilation and lipopolysaccharide‑induced acute lung injury.
Potential mechanism and key genes involved in mechanical ventilation and lipopolysaccharide‑induced acute lung injury.
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机械通气与脂多糖所致急性肺损伤的潜在机制及关键基因
DOI：
10.3892/mmr.2020.11507
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发表时间：
2020-11
影响因子：
3.4
通讯作者：
Jiang L
中科院分区：
文献类型：
--
作者：
Dong WW;Feng Z;Zhang YQ;Ruan ZS;Jiang L
机械通气（MV）和脂多糖（LPS）感染是急性肺损伤的常见原因。本研究的目的是寻找与机械通气（MV）和脂多糖（LPS）诱导的急性肺损伤（ALI）相关的关键基因及其可能的机制。从Gene Expression Omnibus数据库下载患有吸入LPS、MV和LPS + MV诱导的ALI的成年C57 BL/6小鼠的基因表达数据。筛选与MV、LPS和LPS + MV相关的差异表达基因（DEG），进行功能富集分析、蛋白质相互作用网络构建、转录因子预测和小分子药物预测。最后，使用逆转录-定量PCR在体内验证关键基因的表达。分别有63，538和1，635例DEG与MV、LPS和LPS + MV相关。MV相关基因在嘌呤核苷酸代谢过程中显著富集。LPS和LPS + MV相关基因在“细胞对细胞因子刺激的反应”和“细胞趋化性”中显著富集。所有三种条件都富含“TNF信号通路”和“IL-17信号通路”。C-X-C基序趋化因子配体（CXCL）2、CXCL 3和CXCL 10的表达水平在LPS和LPS + MV组中上调。腺苷A2 b受体、锌指和BTB结构域16和羟基羧酸受体2被鉴定为MV组中的DEG。与对照组相比，三组大鼠早期生长反应1和活化型TF 3表达均上调。MV和LPS诱导的ALI既有相似之处，又有不同之处，MV可能增强LPS对基因表达的影响。MV可能影响尿中核糖核苷酸代谢相关过程，而LPS可能引起细胞趋化性和细胞因子刺激反应。炎症反应由MV和LPS共享。本研究结果可为急性肺损伤的研究和治疗提供理论依据。
Mechanical ventilation (MV) and lipopolysaccharide (LPS) infection are common causes of acute lung injury. The aim of the present study was to identify the key genes and potential mechanisms involved in mechanical ventilation (MV) and lipopolysaccharide (LPS)-induced acute lung injury (ALI). Gene expression data of adult C57BL/6 mice with ALI induced by inhaling LPS, MV and LPS + MV were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) associated with MV, LPS and LPS + MV were screened, followed by functional enrichment analysis, protein-protein interaction network construction, and prediction of transcription factors and small molecule drugs. Finally, the expression of key genes was verified in vivo using reverse transcription-quantitative PCR. A total of 63, 538 and 1,635 DEGs were associated with MV, LPS and LPS + MV, respectively. MV-associated genes were significantly enriched in the ‘purine ribonucleotide metabolic process’. LPS and LPS + MV-associated genes were significantly enriched in ‘cellular response to cytokine stimulus’ and ‘cell chemotaxis’. All three conditions were enriched in ‘TNF signaling pathway’ and ‘IL-17 signaling pathway’. Expression levels of C-X-C motif chemokine ligand (CXCL)2, CXCL3 and CXCL10 were upregulated in the LPS and LPS + MV groups. Adenosine A2b receptor, zinc finger and BTB domain-containing 16 and hydroxycarboxylic acid receptor 2 were identified as DEGs in the MV group. Compared with the control group, Early growth response 1 and activating TF 3 was upregulated in all three groups. Similarities and differences were observed among the MV- and LPS-induced ALI, and MV may enhance the effects of LPS on gene expression. MV may affect urine ribonucleotide metabolic-related processes, whereas LPS may cause cell chemotaxis and cytokine stimulus responses in ALI progression. The inflammatory response was shared by MV and LPS. The results of the present study may provide insight into a theoretical basis for the study and treatment of ALI.
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影响因子：
5.1
作者：
Jiang, Wenjiao;Luo, Fen;Ding, Xuansheng
通讯作者：
Ding, Xuansheng
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影响因子：
7.4
作者：
Dong, Wen-Wen;Liu, Yu-Jian;Jiang, Lai
通讯作者：
Jiang, Lai
影响因子：
10.8
作者：
Philipp, Sebastian;Yang, Xi-Ming;Cohen, Michael V.
通讯作者：
Cohen, Michael V.
DOI：
10.1164/rccm.201605-1081cp
发表时间：
2017-02-15
影响因子：
24.7
作者：
Brochard, Laurent;Slutsky, Arthur;Pesenti, Antonio
通讯作者：
Pesenti, Antonio
影响因子：
5.6
作者：
Pedrazza, Leonardo;Cunha, Aline Andrea;de Oliveira, Jarbas Rodrigues
通讯作者：
de Oliveira, Jarbas Rodrigues