Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Jun 26, 2023; 15(6): 293-308
Published online Jun 26, 2023. doi: 10.4330/wjc.v15.i6.293
Identification of potential biomarkers for idiopathic pulmonary fibrosis and validation of TDO2 as a potential therapeutic target
Ru Wang, Yan-Mei Yang
Ru Wang, Henan University of Chinese Medicine, Collaborative Innovation Centre for Chinese Medicine and Respiratory Diseases, Zhengzhou 450046, Henan Province, China
Yan-Mei Yang, Zhengzhou University, Research Centre of Basic Medicine, Academy of Medical Sciences, Zhengzhou 450000, Henan Province, China
Author contributions: Yang YM designed the research study; Wang R and Yang YM performed the research; Yang YM analysed the data and wrote the manuscript; Wang R performed the experiment research; all authors have read and approved the final manuscript.
Institutional review board statement: Our manuscript involves experiments on mice, as well as the A549 and IMR-90 cell lines, but does not involve any human experimentation.
Institutional animal care and use committee statement: The study was reviewed and approved by the Experimental Animal Ethics Committee of Henan University of Chinese Medicine, No. DWLLGZR202202036.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The authors confirm that the data supporting the findings of this study are available.
ARRIVE guidelines statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yan-Mei Yang, PhD, Doctor, Zhengzhou University, Research Centre of Basic Medicine, Academy of Medical Sciences, No. 40 North University Road, Erqi District, Zhengzhou 450000, Henan Province, China. yang_yanmei@gs.zzu.edu.cn
Received: April 14, 2023
Peer-review started: April 14, 2023
First decision: May 17, 2023
Revised: June 1, 2023
Accepted: June 13, 2023
Article in press: June 13, 2023
Published online: June 26, 2023
Processing time: 73 Days and 6 Hours
Abstract
BACKGROUND

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a high mortality rate. On this basis, exploring potential therapeutic targets to meet the unmet needs of IPF patients is important.

AIM

To explore novel hub genes for IPF therapy.

METHODS

Here, we used public datasets to identify differentially expressed genes between IPF patients and healthy donors. Potential targets were considered based on multiple bioinformatics analyses, especially the correlation between hub genes and carbon monoxide diffusing capacity of carbon monoxide, forced vital capacity, and patient survival rate. The mRNA levels of the hub genes were determined through quantitative real-time polymerase chain reaction.

RESULTS

We found that TDO2 was upregulated in IPF patients and predicted poor prognosis. Surprisingly, single-cell RNA sequencing data analysis revealed significant enrichment of TDO2 in alveolar fibroblasts, indicating that TDO2 may participate in the regulation of proliferation and survival. Therefore, we verified the upregulated expression of TDO2 in an experimental mouse model of transforming growth factor-β (TGF-β)-induced pulmonary fibrosis. Furthermore, the results showed that a TDO2 inhibitor effectively suppressed TGF-β-induced fibroblast activation. These findings suggest that TDO2 may be a potential target for IPF treatment. Based on transcription factors-microRNA prediction and scRNA-seq analysis, elevated TDO2 promoted the IPF proliferation of fibroblasts and may be involved in the P53 pathway and aggravate ageing and persistent pulmonary fibrosis.

CONCLUSION

We provided new target genes prediction and proposed blocking TGF-β production as a potential treatment for IPF.

Keywords: Idiopathic pulmonary fibrosis; Lung function; Overall survival; Transforming growth factor-β; TDO2 inhibitor

Core Tip: This study is unique in several aspects: (1) We identified six hub genes for idiopathic pulmonary fibrosis (IPF) and determined through quantitative real-time polymerase chain reaction; (2) Multi-omics analysis proved that TDO2 was upregulated in IPF patients and promoted the IPF proliferation of fibroblasts; (3) TDO2 may be involved in P53 pathway and aggravate aging and persistent pulmonary fibrosis; and (4) TDO2 inhibitor effectively suppressed transforming growth factor-β-induced fibroblast activation.