Division of Life Sciences and Medicine, Department of Rheumatology and Immunology, The First Affiliated Hospital of University of Science and Technology of China (USTC), University of Science and Technology of China, Hefei, PR China.
Division of Life Sciences and Medicine, Stroke Center and Department of Neurology, The First Affiliated Hospital of University of Science and Technology of China (USTC), University of Science and Technology of China, Hefei, PR China.
Rheumatology (Oxford). 2023 Nov 2;62(11):3724-3731. doi: 10.1093/rheumatology/kead117.
DM with positive anti-melanoma differentiation-related gene 5 (MDA5) antibody is an autoimmune disease with multiple complications. Interstitial lung diseases (ILDs) are significantly associated with DM and are particularly related to MDA5+ DM. This article aims to explore potential molecular mechanisms and develop new diagnostic biomarkers for MDA5+ DM-ILD.
The series matrix files of DM and non-specific interstitial pneumonia (NSIP) were downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs). Gene set enrichment analysis (GSEA) was used to screen the common enriched pathways related to DM and NSIP. Next, the co-expressed differential expressed genes (co-DEGs) between MDA5+, MDA5- and NSIP groups were identified by Venn plots, and then selected for different enrichment analyses and protein-protein interaction (PPI) network construction. The mRNA expression levels of IFN-beta and EIF2AK2 were measured by RT-qPCR. The protein expression levels of IFN-beta were measured by ELISA.
Using GSEA, the enriched pathway 'herpes simplex virus 1 infection' was both up-regulated in DM and NSIP. Enrichment analysis in MDA5+ DM, MDA5- DM and NSIP reported that the IFN-beta signalling pathway was an important influencing factor in the MDA5+ DM-ILD. We also identified that eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) was an important gene signature in the MDA5+ DM-ILD by PPI analysis. The expression levels of IFN-beta and EIF2AK2 were significantly increased in MDA5+ DM-ILD patients.
IFN-beta and EIF2AK2 contributed to the pathogenesis of MDA5+ DM-ILD, which could be used as potential therapeutic targets.
抗黑色素瘤分化相关基因 5（MDA5）抗体阳性的糖尿病（DM）是一种伴有多种并发症的自身免疫性疾病。间质性肺疾病（ILDs）与 DM 显著相关，特别是与 MDA5+ DM 相关。本文旨在探讨 MDA5+ DM-ILD 的潜在分子机制并开发新的诊断生物标志物。
从基因表达综合数据库（GEO）下载 DM 和非特异性间质性肺炎（NSIP）的系列矩阵文件，以鉴定差异表达基因（DEGs）。采用基因集富集分析（GSEA）筛选与 DM 和 NSIP 相关的常见富集通路。接下来，通过 Venn 图鉴定 MDA5+、MDA5-和 NSIP 组之间的共表达差异表达基因（co-DEGs），然后进行不同的富集分析和蛋白质-蛋白质相互作用（PPI）网络构建。通过 RT-qPCR 测量 IFN-β 和 EIF2AK2 的 mRNA 表达水平，通过 ELISA 测量 IFN-β 的蛋白表达水平。
使用 GSEA，DM 和 NSIP 中均上调了“单纯疱疹病毒 1 感染”的富集通路。MDA5+ DM、MDA5- DM 和 NSIP 的富集分析报告称，IFN-β 信号通路是 MDA5+ DM-ILD 的一个重要影响因素。通过 PPI 分析，我们还发现真核翻译起始因子 2α 激酶 2（EIF2AK2）是 MDA5+ DM-ILD 的重要基因特征。MDA5+ DM-ILD 患者的 IFN-β 和 EIF2AK2 表达水平显著升高。
IFN-β 和 EIF2AK2 有助于 MDA5+ DM-ILD 的发病机制，可作为潜在的治疗靶点。
