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ID 48671
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著者
Ishikawa, Nobuhisa
Taniwaki, Masaya
Hamai, Kosuke
Iwamoto, Hiroshi 大学院医歯薬保健学研究科(保) 広大研究者総覧
Ohshimo, Shinichiro 大学院医歯薬保健学研究科(医) 広大研究者総覧
Hamada, Hironobu 大学院医歯薬保健学研究科(保) 広大研究者総覧
Hattori, Noboru 大学院医歯薬保健学研究科(医) 広大研究者総覧
Okada, Morihito 原爆放射線医科学研究所 広大研究者総覧
Arihiro, Koji
Ohtsuki, Yuji
Kohno, Nobuoki 大学院医歯薬保健学研究院(医)
抄録(英)
Background: Chronic fibrosing idiopathic interstitial pneumonia (IIP) is characterized by alveolar epithelial damage, activation of fibroblast proliferation, and loss of normal pulmonary architecture and function. This study aims to investigate the genetic backgrounds of IIP through gene expression profiling and pathway analysis, and to identify potential biomarkers that can aid in diagnosis and serve as novel therapeutic targets.
Methods:RNA extracted from lung specimens of 12 patients with chronic fibrosing IIP was profiled using Illumina Human WG-6 v3 BeadChips, and Ingenuity Pathway Analysis was performed to identify altered functional and canonical signaling pathways. For validating the results from gene expression analysis, immunohistochemical staining of 10 patients with chronic fibrosing IIP was performed.
Results: Ninety-eight genes were upregulated in IIP patients relative to control subjects. Some of the upregulated genes, namely desmoglein 3 (DSG3), protocadherin gamma-A9 (PCDHGA9) and discoidin domain-containing receptor 1 (DDR1) are implicated in cell-cell interaction and/or adhesion; some, namely collagen type VII, alpha 1 (COL7A1), contactin-associated protein-like 3B (CNTNAP3B) and mucin-1 (MUC1) are encoding the extracellular matrix molecule or the molecules involved in cell-matrix interactions; and the others, namely CDC25C and growth factor independent protein 1B (GFI1B) are known to affect cell proliferation by affecting the progression of cell cycle or regulating transcription. According to pathway analysis, alternated pathways in IIP were related to cell death and survival and cellular growth and proliferation, which are more similar to cancer than to inflammatory response and immunological diseases. Using immunohistochemistry, we further validate that DSG3, the most highly upregulated gene, shows higher expression in chronic fibrosing IIP lung as compared to control lung.
Conclusion: We identified several genes upregulated in chronic fibrosing IIP patients as compared to control, and found genes and pathways implicated in cancer, rather than in inflammatory or immunological disease to play important roles in the pathogenesis of IIPs. Moreover, DSG3 is a novel potential biomarker for chronic fibrosing IIP with its significantly high expression in IIP lung.
内容記述
This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
掲載誌名
BMC Medical Genetics
18巻
開始ページ
88
出版年月日
2017-08-18
出版者
BioMed Central Ltd
ISSN
1471-2350
出版者DOI
PubMedID
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
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application/pdf
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権利情報
© The Author(s). 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
関連情報URL
部局名
医歯薬保健学研究科
原爆放射線医科学研究所
病院