Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis

Abstract

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.

An explainable machine learning-driven proposal of pulmonary fibrosis biomarkers

“…For instance, AGER , SPP1 , MMP7 and CRLF1 are included in a review list of transcriptionally deregulated genes during IPF compiled by [34] . In addition, genes such as COL1A1 , COL15A1 , COMP , MMP7 and LCN2 were identified as potential IPF drivers by previous exploratory research deliverables comparing the transcriptomes of IPF patients to those of control individuals ( Table 2 ) [35] , [36] , [37] , [38] , [39] .…”

“…3 B), all three strategies seem to have comparable performance as they share 65% of the 1st quartile of the features list. More than half of these common features (8/13) are among the text mining highlighted ones, while four ( COMP , COL1A1 , COL17A1 and COL5A2 ) have been proposed as biomarkers in the past [35] , [36] , [38] , [39] . In addition, comparison of the lists along their whole length using Kendall ranking correlation, revealed strong similarities of BIRRA with each of the SHAP-weighted majority voting and MAIC methods, while the latter two share less common rankings ( Fig.…”

Identification of three hub genes related to the prognosis of idiopathic pulmonary fibrosis using bioinformatics analysis

“…Lamas et al found that the median delay from the onset of clinical symptoms to the first in-hospital diagnosis was approximately 2.2 years, which was associated with a higher rate of death from IPF (P = 0.03) [21] . In the past few years, an increasing number of studies have focused on the cellular and molecular mechanisms of IPF, and progress has been made [22] . Several blood proteins, such as metalloproteases-7 (MMP7), SP-A, and SP-D, can help distinguish IPF from other ILDs, even if they are not included in the guidelines [23][24][25] .…”

Comprehensive analyses of the microRNA–messenger RNA–transcription factor regulatory network in mouse and human renal fibrosis

“…Furthermore, to further verify miRNA conservation between species, sequence analysis was performed and showed that the sequences of miR-125a-3p and miR-199a-5p in mice were identical to those in humans. Strikingly, in patients with IPF, upregulated miR-199a-5p regulated Vegfa and led to the development of IPF or other fibrosis-related diseases ( Zhu et al, 2021 ). Of course, we noticed that many hub genes have no significance in human samples, which may be caused by the differences between species.…”