The molecular mechanism underlying dermatomyositis related interstitial lung disease: evidence from bioinformatic analysis and in vivo validation

Li Zeng; Yiping Tang; Yichen Zhang; Li Yue; Gang Ma; Xumin Ye; Lijing Yang; Kai Chen; Qiao Zhou

doi:10.3389/fimmu.2023.1288098

The molecular mechanism underlying dermatomyositis related interstitial lung disease: evidence from bioinformatic analysis and in vivo validation

Front Immunol. 2023 Oct 19:14:1288098. doi: 10.3389/fimmu.2023.1288098. eCollection 2023.

Authors

Li Zeng¹, Yiping Tang², Yichen Zhang^{3

4}, Li Yue^{3

5}, Gang Ma^{3

5}, Xumin Ye^{3

6}, Lijing Yang^{3

4}, Kai Chen¹, Qiao Zhou^{3

7}

Affiliations

¹ Department of Neurology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
² Department of Internal Medicine, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
³ Department of Rheumatology and Immunology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
⁴ School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
⁵ Chengdu University of Traditional Chinese Medicine, Chengdu, China.
⁶ Southwest Medical University, Luzhou, China.
⁷ Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

Abstract

Background: Dermatomyositis (DM) is an autoimmune and inflammatory disease that can affect the lungs, causing interstitial lung diseases (ILD). However, the exact pathophysiological mechanisms underlying DM-ILD are unknown. Idiopathic pulmonary fibrosis (IPF) belongs to the broader spectrum of ILD and evidence shows that common pathologic pathways might lie between IPF and DM-ILD.

Methods: We retrieved gene expression profiles of DM and IPF from the Gene Expression Omnibus (GEO) and utilized weighted gene co-expression network analysis (WGCNA) to reveal their co-expression modules. We then performed a differentially expressed gene (DEG) analysis to identify common DEGs. Enrichment analyses were employed to uncover the hidden biological pathways. Additionally, we conducted protein-protein interaction (PPI) networks analysis, cluster analysis, and successfully found the hub genes, whose levels were further validated in DM-ILD patients. We also examined the relationship between hub genes and immune cell abundance in DM and IPF. Finally, we conducted a common transcription factors (TFs)-genes network by NetworkAnalyst.

Results: WGCNA revealed 258 intersecting genes, while DEG analysis identified 66 shared genes in DM and IPF. All of these genes were closely related to extracellular matrix and structure, cell-substrate adhesion, and collagen metabolism. Four hub genes (POSTN, THBS2, COL6A1, and LOXL1) were derived through intersecting the top 30 genes of the WGCNA and DEG sets. They were validated as active transcripts and showed diagnostic values for DM and IPF. However, ssGSEA revealed distinct infiltration patterns in DM and IPF. These four genes all showed a positive correlation with immune cells abundance in DM, but not in IPF. Finally, we identified one possible key transcription factor, MYC, that interact with all four hub genes.

Conclusion: Through bioinformatics analysis, we identified common hub genes and shared molecular pathways underlying DM and IPF, which provides valuable insights into the intricate mechanisms of these diseases and offers potential targets for diagnostic and therapeutic interventions.

Keywords: bioinformatic analysis; dermatomyositis; extracellular matrix; idiopathic pulmonary fibrosis; interstitial lung disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Computational Biology
Dermatomyositis* / genetics
Genes, Regulator
Humans
Idiopathic Pulmonary Fibrosis* / genetics
Lung Diseases, Interstitial* / genetics
Transcription Factors / genetics

Substances

Transcription Factors

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study received funding support from the National Natural Science Foundation of China (No. 81801270) and the Sichuan Provincial People’s Hospital (No. 2017QN12).