ID | 63199 |
FullText URL | |
Author |
Higo, Hisao
Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
Ohashi, Kadoaki
Department of Respiratory Medicine, Okayama University Hospital
ORCID
Kaken ID
researchmap
Tomida, Shuta
Center for Comprehensive Genomic Medicine, Okayama University Hospital
Kaken ID
researchmap
Okawa, Sachi
Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
Yamamoto, Hiromasa
Department of Thoracic Surgery, Okayama University Hospital
ORCID
Kaken ID
publons
researchmap
Sugimoto, Seiichiro
Organ Transplant Center, Okayama University Hospital
ORCID
Kaken ID
publons
researchmap
Senoo, Satoru
Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
Makimoto, Go
Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
Ninomiya, Kiichiro
Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
Kaken ID
Nakasuka, Takamasa
Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
Nishii, Kazuya
Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
Taniguchi, Akihiko
Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
Kaken ID
Hotta, Katsuyuki
Center for Innovative Clinical Medicine, Okayama University Hospital
Kaken ID
publons
researchmap
Miyahara, Nobuaki
Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
Kaken ID
publons
researchmap
Maeda, Yoshinobu
Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
Kaken ID
researchmap
Toyooka, Shinichi
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
ORCID
Kaken ID
publons
researchmap
Kiura, Katsuyuki
Department of Respiratory Medicine, Okayama University Hospital
ORCID
Kaken ID
publons
researchmap
|
Abstract | 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.
|
Keywords | Idiopathic pulmonary fibrosis
RNA sequencing
Molecular therapeutic target
Personalized therapy
|
Published Date | 2022-02-07
|
Publication Title |
Respiratory Research
|
Volume | volume23
|
Issue | issue1
|
Publisher | BMC
|
Start Page | 20
|
ISSN | 1465-993X
|
Content Type |
Journal Article
|
language |
English
|
OAI-PMH Set |
岡山大学
|
Copyright Holders | © The Author(s) 2022.
|
File Version | publisher
|
PubMed ID | |
DOI | |
Web of Science KeyUT | |
Related Url | isVersionOf https://doi.org/10.1186/s12931-022-01940-y
|
License | http://creativecommons.org/licenses/by/4.0/
|