Table1_Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease.DOCX

Dermatomyositis (DM), an inflammatory disorder, is often associated with interstitial lung disease (ILD). However, the underlying mechanism remains unclear. Our study performed RNA sequencing (RNA-seq) and integrative bioinformatics analysis of differentially expressed genes (DEGs) in patients with dermatomyositis-associated interstitial lung disease (DM-ILD) and healthy controls. A total of 2,018 DEGs were identified between DM-ILD and healthy blood samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that DEGs were mainly involved in immune- and inflammatory-related biological processes and pathways. Disease ontology (DO) enrichment analysis identified 35 candidate key genes involved in both skin and lung diseases. Meanwhile, a total of 886 differentially expressed alternative splicing (AS) events were found between DM-ILD and healthy blood samples. After overlapping DEGs with differential AS genes, the plasminogen activator and urokinase receptor (PLAUR) involved in immune-related biological processes and complement and coagulation cascades was screened and identified as the most important gene associated with DM-ILD. The protein–protein interaction (PPI) network revealed that PLAUR had interactions with multiple candidate key genes. Moreover, we observed that there were significantly more neutrophils and less naive B cells in DM-ILD samples than in healthy samples. And the expression of PLAUR was significantly positively correlated with the abundance of neutrophils. Significant higher abundance of PLAUR in DM-ILD patients than healthy controls was validated by RT-qPCR. In conclusion, we identified PLAUR as an important player in regulating DM-ILD by neutrophil-associated immune response. These findings enrich our understanding, which may benefit DM-ILD patients.

硬化性肌炎（DM），一种炎症性疾病，常伴发间质性肺疾病（ILD）。然而，其潜在机制尚不明确。本研究对硬化性肌炎相关间质性肺疾病（DM-ILD）患者与健康对照者的差异表达基因（DEGs）进行了RNA测序（RNA-seq）和整合生物信息学分析。在DM-ILD与健康血液样本之间共鉴定出2,018个DEGs。基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析显示，DEGs主要参与免疫和炎症相关的生物学过程和通路。疾病本体（DO）富集分析识别出35个候选关键基因，这些基因与皮肤和肺部疾病均有关。同时，在DM-ILD与健康血液样本之间共发现886个差异表达的可变剪接（AS）事件。通过将DEGs与差异AS基因重叠，筛选并鉴定出参与免疫相关生物学过程和补体及凝血级联反应的纤溶酶原激活剂和尿激酶受体（PLAUR）为与DM-ILD最相关的关键基因。蛋白质-蛋白质相互作用（PPI）网络揭示了PLAUR与多个候选关键基因的相互作用。此外，我们观察到DM-ILD样本中中性粒细胞显著增多，而原始B细胞显著减少，与健康样本相比。PLAUR的表达与中性粒细胞的丰度呈显著正相关。RT-qPCR验证了DM-ILD患者PLAUR的丰度显著高于健康对照者。总之，我们鉴定出PLAUR是调节DM-ILD中与中性粒细胞相关的免疫反应的重要调节因子。这些发现丰富了我们对DM-ILD的理解，可能对DM-ILD患者有益。