Genetic Programs Between Steroid-Sensitive and Steroid-Insensitive Interstitial Lung Disease.

Genetic Programs Between Steroid-Sensitive and Steroid-Insensitive Interstitial Lung Disease.
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DOI:
10.1007/s10753-023-01866-7
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发表时间:
2023-12
期刊:
影响因子:
5.1
通讯作者:
--
中科院分区:
医学2区
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皮质类固醇(GC)的有效性在间质性肺病(ILD)中差异很大。在这项研究中,我们的目的是比较隐源性机化性肺炎(COP),特发性肺纤维化(IPF)和非特异性间质性肺炎(NSIP)患者的基因表达谱,并确定在ILD中负责GC敏感性的分子和途径。选择了三个数据集(GSE 21411、GSE 47460和GSE 32537)。鉴定了COP、IPF、NSIP和健康对照(CTRL)组之间的差异表达基因(DEG)。通过功能富集分析和蛋白质相互作用网络分析,研究DEG的潜在功能。COP与CTRL比较有128个DEG,IPF与CTRL比较有257个DEG,NSIP与CTRL比较有205个DEG,COP与IPF比较有270个DEG。不同ILD组的DEG主要富集于炎症反应。进一步的通路分析显示,“白细胞介素(IL)-17信号通路”(hsa 04657)和“肿瘤坏死因子(TNF)信号通路”与不同类型的ILD相关。共有10个与炎症反应相关的基因被鉴定为枢纽基因,并且它们在IPF组中的表达水平高于COP组。最后,我们确定了两个与GC反应相关的差异表达基因(FOSL 1和DDIT 4)。我们的生物信息学分析表明,炎症反应在ILD的发展中发挥了致病作用。我们还说明了IPF组的炎症反应比COP组更严重,并确定了ILD中两个GC反应相关的差异表达基因(FOSL 1和DDIT 4)。在线版本包含补充材料,可通过10.1007/s10753-023-01866-7获得。
The effectiveness of corticosteroids (GCs) varies greatly in interstitial lung diseases (ILDs). In this study, we aimed to compare the gene expression profiles of patients with cryptogenic organizing pneumonia (COP), idiopathic pulmonary fibrosis (IPF), and non-specific interstitial pneumonia (NSIP) and identify the molecules and pathways responsible for GCs sensitivity in ILDs. Three datasets (GSE21411, GSE47460, and GSE32537) were selected. Differentially expressed genes (DEGs) among COP, IPF, NSIP, and healthy control (CTRL) groups were identified. Functional enrichment analysis and protein–protein interaction network analysis were performed to examine the potential functions of DEGs. There were 128 DEGs when COP versus CTRL, 257 DEGs when IPF versus CTRL, 205 DEGs when NSIP versus CTRL, and 270 DEGs when COP versus IPF. The DEGs in different ILDs groups were mainly enriched in the inflammatory response. Further pathway analysis showed that “interleukin (IL)-17 signaling pathway” (hsa04657) and “tumor necrosis factor (TNF) signaling pathway” were associated with different types of ILDs. A total of 10 genes associated with inflammatory response were identified as hub genes and their expression levels in the IPF group were higher than those in the COP group. Finally, we identified two GCs’ response-related differently expressed genes (FOSL1 and DDIT4). Our bioinformatics analysis demonstrated that the inflammatory response played a pathogenic role in the progression of ILDs. We also illustrated that the inflammatory reaction was more severe in the IPF group compared to the COP group and identified two GCs’ response-related differently expressed genes (FOSL1 and DDIT4) in ILDs. The online version contains supplementary material available at 10.1007/s10753-023-01866-7.
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