Open Access

Molecular differences between stable idiopathic pulmonary fibrosis and its acute exacerbation

Junho Kang1,†,Hye Ju Yeo2,3,†,Yun Hak Kim4,5,*,Woo Hyun Cho2,3,*
Medical Research Institute, Pusan National University, 46240 Busan, Republic of Korea
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, 626-770 Yangsan, Republic of Korea
Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, 626-770 Yangsan, Republic of Korea
Department of Anatomy, School of Medicine, Pusan National University, 50612 Yangsan, Republic of Korea
Department of Biomedical Informatics, School of Medicine, Pusan National University, 50612 Yangsan, Republic of Korea
DOI: 10.52586/5038 Volume 26 Issue 12, pp.1444-1452
Submited: 13 June 2021 Revised: 06 October 2021
Accepted: 25 October 2021 Published: 30 December 2021
*Corresponding Author(s):  
Yun Hak Kim
*Corresponding Author(s):  
Woo Hyun Cho
These authors contributed equally.
Copyright: © 2021 The author(s). Published by BRI. This is an open access article under the CC BY 4.0 license (

Introduction: The molecular mechanisms underlying acute exacerbations (AEs) of idiopathic pulmonary fibrosis (IPF) are poorly understood. To understand the gene expression patterns of the AEs of IPF, we studied gene expression profiling of AEs of IPF. Methods: The GEO datasets included in this study are GSE44723 and GSE10667, and in-house RNA-seq data were used. DEG analysis used the limma package, and the STRING database was used to construct the protein-protein interaction (PPI) network, and its functional role was investigated through gene ontology analysis. Results: The results of DEG analysis indicated 76 upregulated and 135 downregulated genes associated with an AE of IPF compared to stable IPF. The PPI network included three core modules containing 24 of the 211 DEGs. Eleven upregulated and six downregulated genes were evident in AEs of IPF compared with stable IPF after validation. The upregulated genes were associated with cell division. The downregulated genes were related to skeletal muscle differentiation and development. Conclusion: In previous studies, 17 genes were strongly associated with cell proliferation in various cell types. In particular, cyclin A2 (CCNA2) was overexpressed in the alveolar epithelium of the lungs presenting AEs of IPF. Aside from the previously described CCNA2, this study reveals 16 genes associated with AEs of IPF. This data could indicate new therapeutic targets and potential biomarkers for the AEs of IPF.

Key words

IPF; Acute exacerbation; Transplantation; RNA sequencing


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Junho Kang, Hye Ju Yeo, Yun Hak Kim, Woo Hyun Cho. Molecular differences between stable idiopathic pulmonary fibrosis and its acute exacerbation. Frontiers in Bioscience-Landmark. 2021. 26(12); 1444-1452.