Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis

Hui Zhao; Lan Wang; Yi Yan; Qin-Hua Zhao; Jing He; Rong Jiang; Ci-Jun Luo; Hong-Ling Qiu; Yu-Qing Miao; Su-Gang Gong; Ping Yuan; Wen-Hui Wu

doi:10.3389/fimmu.2023.1197752

Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis

Front Immunol. 2023 Sep 4:14:1197752. doi: 10.3389/fimmu.2023.1197752. eCollection 2023.

Authors

Hui Zhao^{1

2}, Lan Wang¹, Yi Yan^{1

3}, Qin-Hua Zhao¹, Jing He¹, Rong Jiang¹, Ci-Jun Luo¹, Hong-Ling Qiu¹, Yu-Qing Miao², Su-Gang Gong¹, Ping Yuan¹, Wen-Hui Wu¹

Affiliations

¹ Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
² School of Materials and Chemistry & Institute of Bismuth and Rhenium, University of Shanghai for Science and Technology, Shanghai, China.
³ Heart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Pulmonary fibrosis (PF) and pulmonary hypertension (PH) have common pathophysiological features, such as the significant remodeling of pulmonary parenchyma and vascular wall. There is no effective specific drug in clinical treatment for these two diseases, resulting in a worse prognosis and higher mortality. This study aimed to screen the common key genes and immune characteristics of PF and PH by means of bioinformatics to find new common therapeutic targets. Expression profiles are downloaded from the Gene Expression Database. Weighted gene co-expression network analysis is used to identify the co-expression modules related to PF and PH. We used the ClueGO software to enrich and analyze the common genes in PF and PH and obtained the protein-protein interaction (PPI) network. Then, the differential genes were screened out in another cohort of PF and PH, and the shared genes were crossed. Finally, RT-PCR verification and immune infiltration analysis were performed on the intersection genes. In the result, the positive correlation module with the highest correlation between PF and PH was determined, and it was found that lymphocyte activation is a common feature of the pathophysiology of PF and PH. Eight common characteristic genes (ACTR2, COL5A2, COL6A3, CYSLTR1, IGF1, RSPO3, SCARNA17 and SEL1L) were gained. Immune infiltration showed that compared with the control group, resting CD4 memory T cells were upregulated in PF and PH. Combining the results of crossing characteristic genes in ImmPort database and RT-PCR, the important gene IGF1 was obtained. Knocking down IGF1 could significantly reduce the proliferation and apoptosis resistance in pulmonary microvascular endothelial cells, pulmonary smooth muscle cells, and fibroblasts induced by hypoxia, platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-β1 (TGF-β1), respectively. Our work identified the common biomarkers of PF and PH and provided a new candidate gene for the potential therapeutic targets of PF and PH in the future.

Keywords: T cells CD4; WGCNA; differential gene analysis; pulmonary fibrosis; pulmonary hypertension.

Publication types

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

MeSH terms

Computational Biology
Endothelial Cells
Genes, Regulator
Humans
Hypertension, Pulmonary* / genetics
Proteins
Pulmonary Fibrosis* / genetics

Substances

SEL1L protein, human
Proteins

Grants and funding

This work was supported by the Program of National Natural Science Foundation of China (81900050, 82000059), the Program of Natural Science Foundation of Shanghai (22ZR1452400), the Pujiang Talent Program (22PJD064), the Special Youth Program of Clinical Research in Health Industry of Shanghai Health and Wellness Committee (20204Y0384) and the Program of Shanghai Pulmonary Hospital (fk18003, fkly20005).