THE CRITICAL ROLE OF THE HISTONE MODIFICATION ENZYME SETDB2 IN THE PATHOGENESIS OF ACUTE RESPIRATORY DISTRESS SYNDROME

• Material Type: 博士論文
• Title: THE CRITICAL ROLE OF THE HISTONE MODIFICATION ENZYME SETDB2 IN THE PATHOGENESIS OF ACUTE RESPIRATORY DISTRESS SYNDROME
• Author/Editor: Sonobe, Shota; Kitabatake, Masahiro; Hara, Atsushi; Konda, Makiko; Ouji-Sageshima, Noriko; Terada-Ikeda, Chiyoko; Furukawa, Ryutaro; Imakita, Natsuko; Oda, Akihisa; Takeda, Maiko; Takamura, Shiki; Inoue, Satoki; Steven, L. Kunkel; Kawaguchi, Masahiko; Ito, Toshihiro
• Author Heading: Sonobe, Shota; Kitabatake, Masahiro; Hara, Atsushi; Konda, Makiko; Ouji-Sageshima, Noriko; Terada-Ikeda, Chiyoko; Furukawa, Ryutaro; Imakita, Natsuko; Oda, Akihisa; Takeda, Maiko; Takamura, Shiki; Inoue, Satoki; Steven, L. Kunkel; Kawaguchi, Masahiko; Ito, Toshihiro
• Publication, Distribution, etc.: Lippincott, Williams & Wilkins
• Publication Date: 2023-07
• Publication Date (W3CDTF): 2023-07
• Alternative Title: 急性呼吸促迫症候群の病態におけるヒストン修飾酵素Setdb2の重要な役割
• Periodical title: Shock
• No. or year of volume/issue: 60 1
• Volume: 60
• Issue: 1
• Pages: 137-145
• ISSN (Periodical Title): ISSN : 1540-0514
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2023-09-29
• Dissertation Number: 甲第888号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Epigenetics; acute respiratory distress syndrome; apoptosis; endothelial cell; macrophage; SET domain bifurcated 2
• Target Audience: 一般
• Note (General): type:Thesis; Introduction: Acute respiratory distress syndrome (ARDS) is a severe hypoxemic respiratory failure with a high in-hospital mortality. However, themolecular mechanisms underlying ARDS remain unclear. Recent findings have indicated that the onset of severe inflammatory diseases, such as sepsis, is regulated by epigenetic changes. We investigated the role of epigenetic changes in ARDS pathogenesis using mouse models and human samples. Methods: Acute respiratory distress syndrome was induced in a mouse model (C57BL/6 mice, myeloid cell or vascular endothelial cell [VEC]–specific SET domain bifurcated 2 [Setdb2]–deficient mice [Setdb2ffLyz2Cre+ or Setdb2ffTie2Cre+], and Cre− littermates) by intratracheal administration of lipopolysaccharide (LPS). Analyses were performed at 6 and 72 h after LPS administration. Sera and lung autopsy specimens from ARDS patients were examined. Results: In the murine ARDS model, we observed high expression of the histone modification enzyme SET domain bifurcated 2 (Setdb2) in the lungs. In situ hybridization examination of the lungs revealed Setdb2 expression in macrophages and VECs. The histological score and albumin level of bronchoalveolar lavage fluid were significantly increased in Setdb2ffTie2Cre+ mice following LPS administration compared with Setdb2ffTie2Cre- mice, whereas there was no significant difference between the control and Setdb2ffLyz2Cre+ mice. Apoptosis of VECs was enhanced in Setdb2ffTie2Cre+ mice. Among the 84 apoptosis-related genes, the expression of TNF receptor superfamily member 10b (Tnfrsf10b) was significantly higher in Setdb2ffTie2Cre+ mice than in control mice. Acute respiratory distress syndrome patients' serum showed higher SETDB2 levels than those of healthy volunteers. SETDB2 levels were negatively correlated with the partial pressure of oxygen in arterial blood/fraction of inspiratory oxygen concentration ratio. Conclusion: Acute respiratory distress syndrome elevates Setdb2, apoptosis of VECs, and vascular permeability. Elevation of histone methyltransferase Setdb2 suggests the possibility to histone change and epigenetic modification. Thus, Setdb2 may be a novel therapeutic target for controlling the pathogenesis of ARDS.; 権利情報：© 2023 The Author(s). Published byWolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.; identifier:Shock. 2023 Jul, vol.60, no.1, p.137-145; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4218; identifier:Shock, 60(1): 137-145
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1097/SHK.0000000000002145
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4218/1/K888%20full.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4218/2/K888_abstract.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4218/3/K888_review.pdf fulltext