Related Experiment Video
Updated: Jan 28, 2026
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
Gene Expression Changes Associated with Nintedanib Treatment in Idiopathic Pulmonary Fibrosis Fibroblasts: A
Chau-Chyun Sheu1,2,3, Wei-An Chang4,5,6, Ming-Ju Tsai7,8,9
1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. sheucc@gmail.com.
Abstract:
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease. Therapeutic options for IPF remain limited. Nintedanib, a tyrosine kinase inhibitor approved for IPF treatment, is known to inhibit fibroblasts proliferation, migration and transformation to myofibroblasts. However, how nintedanib changes gene regulations in IPF has never been systematically investigated. We conducted a next-generation sequencing and bioinformatics study to evaluate the changes of mRNA and miRNA profiles in IPF fibroblasts treated with 2 µM and 4 µM nintedanib, compared to those without treatment. We identified 157 upregulated and 151 downregulated genes and used STRING and DAVID databases for analysis of protein⁻protein interactions, biological pathways, and molecular functions. We found strong protein⁻protein interactions within these dysregulated genes, mostly involved in the pathways of cell cycle and mitotic cell cycle. We also discovered 13 potential miRNA⁻mRNA interactions associated with nintedanib treatment. After validation using miRDB, TargetScan, and RT-qPCR, we identified 4 downregulated genes (DDX11, E2F1, NPTX1, and PLXNA4) which might be repressed by the upregulated hsa-miR-486-3p. According to the proposed functions of DDX11, E2F1, and PLXNA4 reported in previous studies, these gene expression changes together might contribute to decreased proliferation of fibroblasts and decreased angiogenesis in the microenvironment of IPF. Our findings need further studies to confirm.
Insights
Nintedanib, a treatment for idiopathic pulmonary fibrosis (IPF), alters gene expression in lung fibroblasts. This study reveals how nintedanib impacts mRNA and miRNA profiles, potentially inhibiting fibroblast proliferation and angiogenesis in IPF.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Bioinformatics
Background:
- Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with limited treatment options.
- Nintedanib is an approved tyrosine kinase inhibitor for IPF, known to affect fibroblast behavior.
- The precise gene regulatory mechanisms of nintedanib in IPF remain unelucidated.
Purpose of the Study:
- To systematically investigate the changes in mRNA and miRNA profiles in IPF fibroblasts upon nintedanib treatment.
- To identify specific genes and microRNAs (miRNAs) involved in nintedanib's therapeutic effects.
- To explore the molecular pathways and interactions affected by nintedanib in IPF.
Main Methods:
- Next-generation sequencing (NGS) to analyze mRNA and miRNA expression profiles.
- Bioinformatic analyses using STRING and DAVID databases for pathway and interaction analysis.
- Validation of identified miRNA-mRNA interactions using miRDB, TargetScan, and RT-qPCR.
Main Results:
- Identified 157 upregulated and 151 downregulated genes in nintedanib-treated IPF fibroblasts.
- Discovered strong protein-protein interactions among dysregulated genes, primarily in cell cycle pathways.
- Identified 4 downregulated genes (DDX11, E2F1, NPTX1, PLXNA4) potentially repressed by upregulated hsa-miR-486-3p.
Conclusions:
- Nintedanib treatment significantly alters gene expression in IPF fibroblasts.
- The identified gene expression changes, particularly involving hsa-miR-486-3p, may contribute to reduced fibroblast proliferation and angiogenesis.
- These findings provide novel insights into nintedanib's mechanism of action in IPF, warranting further investigation.
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