Int J Med Sci 2021; 18(15):3412-3424. doi:10.7150/ijms.61309 This issue

Research Paper

Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis

Ke Zhu1*, Aiqun Xu2*, Wanli Xia3*, Pulin Li1, Rui Han1, Enze Wang1, Sijing Zhou4,5, Ran Wang1✉

1. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
2. Department of General Medicine, Hefei Second People's Hospital, Hefei 230001, China
3. Department of Thoracic Surgery, the first affiliated hospital of Anhui medical university, Hefei 230022, China
4. Hefei Third Clinical College of Anhui Medical University, Hefei 230022, China.
5. Hefei Prevention and Treatment Center for Occupational Diseases, Hefei 230022, China.
*Ke Zhu, Aiqun Xu and Wanli Xia contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Zhu K, Xu A, Xia W, Li P, Han R, Wang E, Zhou S, Wang R. Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis. Int J Med Sci 2021; 18(15):3412-3424. doi:10.7150/ijms.61309. Available from

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Graphic 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.

Keywords: IPF, Lung tissue, Genes, microRNAs, Bioinformatics