Zheng Lanzhi, Zhang Zhuoyi, Song Kang, Xu Xiaoyang, Tong Yixin, Wei Jinling, Jiang Lu
Emergency Department, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou City, 310006 Zhejiang Province, China.
Emergency Department, The First Affiliated Hospital of Zhejiang Chinese Medical University, Youdian Road 54#, Shangcheng District, Hangzhou City, 310006 Zhejiang Province, China.
Open Med (Wars). 2022 Jun 8;17(1):1066-1076. doi: 10.1515/med-2022-0491. eCollection 2022.
Acute lung injury (ALI) is a severe respiratory disorder occurring in critical care medicine, with high rates of mortality and morbidity. This study aims to screen the potential biomarkers for ALI. Microarray data of lung tissues from lung-specific geranylgeranyl pyrophosphate synthase large subunit 1 knockout and wild-type mice treated with lipopolysaccharide were downloaded. Differentially expressed genes (DEGs) between ALI and wild-type mice were screened. Functional analysis and the protein-protein interaction (PPI) modules were analyzed. Finally, a miRNA-transcription factor (TF)-target regulation network was constructed. Totally, 421 DEGs between ALI and wild-type mice were identified. The upregulated DEGs were mainly enriched in the peroxisome proliferator-activated receptor signaling pathway, and fatty acid metabolic process, while downregulated DEGs were related to cytokine-cytokine receptor interaction and regulation of cytokine production. , , , and were key nodes in the PPI network. In addition, three miRNAs (miR505, miR23A, and miR23B) and three TFs (PU1, CEBPA, and CEBPB) were key molecules in the miRNA-TF-target network. Nine genes including , , , , and were predicted as potential druggable genes. As a conclusion, , , , , , , and might be novel markers and potential druggable genes in ALI by regulating inflammatory response.
急性肺损伤（ALI）是危重症医学中发生的一种严重呼吸系统疾病，死亡率和发病率很高。本研究旨在筛选ALI的潜在生物标志物。下载了肺特异性香叶基香叶基焦磷酸合酶大亚基1敲除小鼠和经脂多糖处理的野生型小鼠肺组织的微阵列数据。筛选了ALI小鼠和野生型小鼠之间的差异表达基因（DEG）。进行了功能分析和蛋白质-蛋白质相互作用（PPI）模块分析。最后，构建了一个miRNA-转录因子（TF）-靶标调控网络。共鉴定出ALI小鼠和野生型小鼠之间的421个DEG。上调的DEG主要富集在过氧化物酶体增殖物激活受体信号通路和脂肪酸代谢过程中，而下调的DEG与细胞因子-细胞因子受体相互作用和细胞因子产生的调节有关。 、 、 、 和 是PPI网络中的关键节点。此外，三种miRNA（miR505、miR23A和miR23B）和三种TF（PU1、CEBPA和CEBPB）是miRNA-TF-靶标网络中的关键分子。包括 、 、 、 、 和 在内的九个基因被预测为潜在的可成药基因。结论是， 、 、 、 、 、 、 和 可能通过调节炎症反应成为ALI中的新型标志物和潜在的可成药基因。
