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Updated: Oct 4, 2025

Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
Identification of targetable kinases in idiopathic pulmonary fibrosis
Hisao Higo1, Kadoaki Ohashi2, Shuta Tomida3
1Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan.
Background:
Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF).
Methods:
Thirteen samples from five patients with IPF (Cases 1-5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n = 13) and control samples (n = 8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC).
Results:
Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions.
Conclusions:
We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. We found that DCLK1 and STK33 may serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK might also serve as personalized therapeutic targets of IPF. Additional large-scale studies are warranted to develop personalized therapies for patients with IPF.
Insights
This study identified DCLK1 and STK33 as potential therapeutic targets for idiopathic pulmonary fibrosis (IPF). Other kinases like PDK4, ERBB4, PIM2, and SYK may offer personalized IPF treatment options.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Oncology
Background:
- Tyrosine kinase activation is crucial in pulmonary fibrosis progression.
- Idiopathic pulmonary fibrosis (IPF) requires novel therapeutic targets.
- Kinase gene expression profiling can identify potential IPF treatments.
Purpose of the Study:
- To analyze kinase gene expression in IPF lung tissue.
- To identify potential molecular targets for IPF therapy.
- To explore personalized treatment strategies for IPF.
Main Methods:
- Next-generation sequencing of 612 kinase and cancer-related genes.
- Analysis of 13 IPF lung tissue samples and 8 control samples.
- Confirmation of gene expression using immunohistochemistry (IHC).
Main Results:
- Gene expression correlated with fibrosis severity (Ashcroft score).
- IPF lung samples showed greater heterogeneity than controls.
- DCLK1 and STK33 were upregulated in IPF samples; other kinases varied by case.
Conclusions:
- DCLK1 and STK33 are promising targets for IPF molecular therapy.
- PDK4, ERBB4, PIM2, and SYK may serve as personalized IPF targets.
- Further large-scale studies are needed for personalized IPF therapies.
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