Identification of IPF specific genes expressed by lung tissue-derived fibroblasts using next generation sequencing

Eun-Jeong Seo; Jong-Uk Lee; Seung-Lee Park; Min-Kyung  Kim; Jae-Sung  Choi; Hun-Gyu  Hwang; Jung-Hyun  Kim; Hun-Soo  Chang; Choon-Sik Park

doi:10.36141/svdld.2026.17698

Authors

Eun-Jeong Seo Department of Interdisciplinary Program in Biomedical Science Major, Graduate School, Soonchunhyang University, Asan, Republic of Korea https://orcid.org/0009-0000-9347-0244
Jong-Uk Lee Department of Interdisciplinary Program in Biomedical Science Major, Graduate School, Soonchunhyang University, Asan, Republic of Korea https://orcid.org/0000-0002-0232-5381
Seung-Lee Park Department of Interdisciplinary Program in Biomedical Science Major, Graduate School, Soonchunhyang University, Asan, Republic of Korea https://orcid.org/0000-0002-1562-732X
Min-Kyung Kim Department of Interdisciplinary Program in Biomedical Science Major, Graduate School, Soonchunhyang University, Asan, Republic of Korea https://orcid.org/0000-0003-2996-0198
Jae-Sung Choi Division of Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea https://orcid.org/0000-0002-8673-8131
Hun-Gyu Hwang Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea https://orcid.org/0000-0001-9304-7219
Jung-Hyun Kim Division of Allergy and Clinical Immunology, Department of Internal Medicine, Soonchunhyang University Hospital, Seoul, Republic of Korea https://orcid.org/0000-0002-5498-5170
Hun-Soo Chang Department of Interdisciplinary Program in Biomedical Science Major, Graduate School, Soonchunhyang University, Asan, Republic of Korea https://orcid.org/0000-0002-4025-4182
Choon-Sik Park Biobank, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea https://orcid.org/0000-0001-7955-2526

Keywords:

idiopathic Pulmonary Fibrosis (IPF), Fibroblast, Gene expression profiling, Extracellular Matrix

Abstract

Background and aim: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by aberrant fibroblast activation and excessive extracellular matrix (ECM) accumulation, resulting in irreversible lung remodeling. Although fibroblasts are central to IPF pathogenesis, comprehensive transcriptomic analyses of IPF patient-derived lung fibroblasts remain limited. This study aimed to identify novel molecular contributors to IPF through transcriptomic profiling of lung fibroblasts.

Methods: We performed total RNA sequencing on primary lung fibroblasts isolated from 33 IPF patients and 10 controls, the latter derived from histologically normal lung tissue adjacent to resected tumors. Differentially expressed genes (DEGs) were identified using trimmed mean of M-values normalization and the Exact test with Bonferroni correction. Gene ontology (GO) enrichment was conducted using DAVID, and network analyses were conducted via STRING and GeneClip3.

Results: GO analysis of 475 DEGs (402 upregulated, 73 downregulated) revealed strong enrichment in ECM-related terms consistently observed across three prior IPF fibroblast datasets. Pathway analysis further implicated cytokine–cytokine receptor interaction, complement and coagulation cascades, and immune-related processes. Network analysis identified SERPING1, NR4A1, and C3 as shared hub genes across both STRING and GeneClip3 platforms. Of the top 20 DEGs, 15 had prior associations with fibrosis, while, six (HSD17B2, HMGCLL1, RASL12, HBG1, LOC105375566 and RIPOR3-AS1) were novel. OAS2, an interferon-stimulated gene, emerged as a novel immune-fibrotic axis component in IPF.

Conclusions: This transcriptomic analysis confirms ECM dysregulation as a core feature of IPF pathogenesis and highlights novel DEGs and hub genes with potential roles in fibrosis, providing a foundation for future functional and translational studies.

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