ID | 62249 |
フルテキストURL | |
著者 |
Hatipoglu, Omer Faruk
Department of Pharmacology, Faculty of Medicine, Kindai University
Uctepe, Eyyup
Acıbadem Labmed Ankara Tissue Typing Laboratory
Opoku, Gabriel
Department of Medical Technology, Graduate School of Health Sciences, Okayama University
Wake, Hidenori
Department of Pharmacology, Faculty of Medicine, Kindai University
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Ikemura, Kentaro
Department of Medical Technology, Graduate School of Health Sciences, Okayama University
Ohtsuki, Takashi
Department of Medical Technology, Graduate School of Health Sciences, Okayama University
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Inagaki, Junko
Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Gunduz, Mehmet
Department of Otolaryngology, Moriya Keiyu Hospital
Gunduz, Esra
Department of Otolaryngology, Moriya Keiyu Hospital
Watanabe, Shogo
Department of Medical Technology, Graduate School of Health Sciences, Okayama University
Nishinaka, Takashi
Department of Pharmacology, Faculty of Medicine, Kindai University
Takahashi, Hideo
Department of Pharmacology, Faculty of Medicine, Kindai University
Hirohata, Satoshi
Department of Medical Technology, Graduate School of Health Sciences, Okayama University
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抄録 | Idiopathic pulmonary fibrosis (IPF) is the most common and most deadly form of interstitial lung disease. Osteopontin (OPN), a matricellular protein with proinflammatory and profibrotic properties, plays a major role in several fibrotic diseases, including IPF; OPN is highly upregulated in patients' lung samples. In this study, we knocked down OPN in a bleomycin (BLM)-induced pulmonary fibrosis (PF) mouse model using small interfering RNA (siRNA) to determine whether the use of OPN siRNA is an effective therapeutic strategy for IPF. We found that fibrosing areas were significantly smaller in specimens from OPN siRNA-treated mice. The number of alveolar macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage fluid was also reduced in OPN siRNA-treated mice. Regarding the expression of epithelial-mesenchymal transition (EMT)-related proteins, the administration of OPN-siRNA to BLM-treated mice upregulated E-cadherin expression and downregulated vimentin expression. Moreover, in vitro, we incubated the human alveolar adenocarcinoma cell line A549 with transforming growth factor (TGF)-beta 1 and subsequently transfected the cells with OPN siRNA. We found a significant upregulation of Col1A1, fibronectin, and vimentin after TGF-beta 1 stimulation in A549 cells. In contrast, a downregulation of Col1A1, fibronectin, and vimentin mRNA levels was observed in TGF-beta 1-stimulated OPN knockdown A549 cells. Therefore, the downregulation of OPN effectively reduced pulmonary fibrotic and EMT changes both in vitro and in vivo. Altogether, our results indicate that OPN siRNA exerts a protective effect on BLM-induced PF in mice. Our results provide a basis for the development of novel targeted therapeutic strategies for IPF.
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キーワード | Pulmonary fibrosis
Osteopontin
Epithelial-mesenchymal transition
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発行日 | 2021-07
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出版物タイトル |
Biomedicine & Pharmacotherapy
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巻 | 139巻
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出版者 | Elsevier France-Editions Scientifiques Medicales e
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開始ページ | 111633
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ISSN | 0753-3322
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2021 The Author(s).
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論文のバージョン | publisher
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DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1016/j.biopha.2021.111633
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ライセンス | http://creativecommons.org/licenses/by/4.0/
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助成機関名 |
Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK)
日本学術振興会
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助成番号 | 113S947
20H00548
17K11009
19K09627
19K11791
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