Acta Reumatol Port. 2020 Jul-Sep;45(3):191-200.
Pulmonary complications, including pulmonary fibrosis, are the leading causes of death in systemic sclerosis(SSc). However, the aetiology and pathophysiologic mechanisms of the disease have not been comprehensively investigated, and drugs for treating systemic sclerosis-associated interstitial lung disease (SSc-ILD) are limited. The objective of this study was to identify key novel genes and pathways linked to SSc-ILD and decipher the molecular mechanisms involved in the disease.
We compared three microarray datasets in the GEO database including 42 SSc-ILD samples and 18 normal samples to obtain differentially expressed genes (DEGs). Gene Ontology (GO) analysis and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis were performed, and a protein-protein interaction network was constructed. After validation, gene set enrichment analysis (GSEA) was applied to obtain further insights into the function of the selected hub genes.
A total of 25 DEGs were filtered. The GO analysis revealed genes that were mainly enriched in immune response, chemokine activity, and extracellular regions. KEGG pathway analysis of the DEGs revealed that SSc-ILD was associated with the tumour necrosis factor (TNF) signalling pathway and cytokine-cytokine receptor interaction. Matrix metallopeptidase 7 (MMP7) expression was consistently increased in all the three datasets, and results of the GSEA indicated that MMP7 might play a role in the regulation of the G-protein coupled amine receptor activity.
In summary, the novel DEGs, especially MMP7 and the SSc-ILD pathway genes identified in this study might provide further insights into potential molecular mechanism of the disease.
肺并发症，包括肺纤维化，是系统性硬皮病（SSc）死亡的主要原因。然而，该疾病的病因和病理生理机制尚未得到全面研究，且治疗系统性硬皮病相关间质性肺病（SSc-ILD）的药物有限。本研究旨在确定与 SSc-ILD 相关的关键新基因和途径，并阐明疾病涉及的分子机制。
我们比较了 GEO 数据库中的三个微阵列数据集，包括 42 个 SSc-ILD 样本和 18 个正常样本，以获得差异表达基因（DEGs）。进行基因本体论（GO）分析和京都基因与基因组百科全书（KEGG）途径分析，并构建蛋白质-蛋白质相互作用网络。验证后，进行基因集富集分析（GSEA），以进一步了解所选枢纽基因的功能。
共筛选出 25 个 DEG。GO 分析表明，这些基因主要富集在免疫反应、趋化因子活性和细胞外区。DEGs 的 KEGG 途径分析表明，SSc-ILD 与肿瘤坏死因子（TNF）信号通路和细胞因子-细胞因子受体相互作用有关。基质金属蛋白酶 7（MMP7）在所有三个数据集均持续上调，且 GSEA 结果表明，MMP7 可能在 G 蛋白偶联胺受体活性的调节中发挥作用。
总之，本研究中鉴定的新 DEG，尤其是 MMP7 和 SSc-ILD 途径基因，可能为该疾病的潜在分子机制提供进一步的见解。
