Rationale: Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of idiopathic interstitial pneumonia. Some miRNAs may be associated with IPF and may affect the occurrence and development of IPF in various pathways. Many miRNAs and genes that may be involved in the development of IPF have been discovered using chip and high throughput technologies. Methods: We analyzed one miRNA and four mRNA databases. We identified hub genes and pathways related to IPF using GO, KEGG enrichment analysis, gene set variation analysis (GSVA), PPI network construction, and hub gene analysis. A comprehensive analysis of differentially expressed miRNAs (DEMs), predicted miRNA target genes, and differentially expressed genes (DEGs) led to the creation of a miRNA-mRNA regulatory network in IPF. Results: We found 203 DEGs and 165 DEMs that were associated with IPF. The findings of enrichment analyses showed that these DEGs were mainly involved in antimicrobial humoral response, antimicrobial humoral immune response mediated by antimicrobial peptide, extracellular matrix organization, cell killing, and organ or tissue specific immune response. The VEGFA, CDH5, and WNT3A genes overlapped between hub genes and the miRNA-mRNA regulatory network. The miRNAs including miR-199b-5p, miR-140-5p, miR-199a-5p, miR-125A-5p, and miR-107 that we predicted would regulate the VEGFA, CDH5, and WNT3A genes, which were also associated with IPF or other fibrosis-related diseases. GSVA indicated that metabolic processes of UTP and IMP, immune response, regulation of Th2 cell cytokine production, and positive regulation of NK cell-mediated immunity are associated with the pathogenesis and treatment of IPF. These pathways also interact with VEGFA, CDH5, and WNT3A. Conclusion: These findings provide a new research direction for the diagnosis and treatment of IPF.

中文翻译：

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特发性肺纤维化分子机制的综合分析。

基本原理：特发性肺纤维化 (IPF) 是特发性间质性肺炎最具侵袭性的形式之一。一些miRNA可能与IPF相关，并可能通过多种途径影响IPF的发生和发展。已经使用芯片和高通量技术发现了许多可能参与 IPF 发展的 miRNA 和基因。方法：我们分析了一个 miRNA 和四个 mRNA 数据库。我们使用 GO、KEGG 富集分析、基因集变异分析 (GSVA)、PPI 网络构建和中枢基因分析确定了与 IPF 相关的中枢基因和通路。对差异表达 miRNA (DEM)、预测的 miRNA 靶基因和差异表达基因 (DEG) 的综合分析导致在 IPF 中创建 miRNA-mRNA 调控网络。结果：我们发现了与 IPF 相关的 203 个 DEG 和 165 个 DEM。富集分析结果表明，这些DEGs主要参与抗菌体液反应、抗菌肽介导的抗菌体液免疫反应、细胞外基质组织、细胞杀伤以及器官或组织特异性免疫反应。VEGFA、CDH5 和 WNT3A 基因在中枢基因和 miRNA-mRNA 调控网络之间重叠。我们预测的包括 miR-199b-5p、miR-140-5p、miR-199a-5p、miR-125A-5p 和 miR-107 在内的 miRNA 会调节 VEGFA、CDH5 和 WNT3A 基因，这些基因也与IPF 或其他纤维化相关疾病。GSVA 表明 UTP 和 IMP 的代谢过程、免疫反应、Th2 细胞细胞因子产生的调节、NK细胞介导免疫的正向调节与IPF的发病机制和治疗有关。这些途径还与 VEGFA、CDH5 和 WNT3A 相互作用。结论：这些发现为IPF的诊断和治疗提供了新的研究方向。