A disintegrin and metalloproteinase with thrombospondin motifs 4 regulates pulmonary vascular hyperpermeability through destruction of glycocalyx in acute respiratory distress syndrome 22

• 資料種別: 博士論文
• タイトル: A disintegrin and metalloproteinase with thrombospondin motifs 4 regulates pulmonary vascular hyperpermeability through destruction of glycocalyx in acute respiratory distress syndrome
• 巻次・部編番号: 24 22
• 著者・編者: Konda, Makiko; Kitabatake, Masahiro; Ouji-Sageshima, Noriko; Tonomura, Rei; Furukawa, Ryutaro; Sonobe, Shota; Terada-Ikeda, Chiyoko; Takeda, Maiko; Kawaguchi, Masahiko; Ito, Toshihiro
• 著者標目: Konda, Makiko; Kitabatake, Masahiro; Ouji-Sageshima, Noriko; Tonomura, Rei; Furukawa, Ryutaro; Sonobe, Shota; Terada-Ikeda, Chiyoko; Takeda, Maiko; Kawaguchi, Masahiko; Ito, Toshihiro
• 出版事項: MDPI
• 出版年月日等: 2023-11; 24 22
• 出版年（W3CDTF）: 2023-11
• 並列タイトル等: ADAMTS4は急性呼吸窮迫症候群においてグリコカリックスを介した肺血管透過性亢進を制御する
• タイトル（掲載誌）: International Journal of Molecular Sciences
• 掲載ページ: 16230-
• ISSN（掲載誌）: 16616596
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2024-03-14
• 授与年月日（W3CDTF）: 2024-03-14
• 報告番号: 甲第906号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: ADAMTS4; ARDS; endothelial cells; glycocalyx; vascular permeability
• 対象利用者: 一般
• 一般注記: type:Thesis; Acute respiratory distress syndrome (ARDS) has no specific and effective treatment, and there is an urgent need to understand its pathogenesis. Therefore, based on the hypothesis that molecules whose expression is upregulated in injured pulmonary vascular endothelial cells (VECs) are involved in the pathogenesis of ARDS, we conducted a study to elucidate the molecular mechanisms and identify target factors for treatment. Primary human lung microvascular endothelial cells (HMVEC-Ls) were stimulated with lipopolysaccharide (LPS) or poly (I:C) and analyzed via a microarray to identify target genes for ARDS. We found that a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) was induced in murine lung VECs in an LPS-mediated ARDS model. Elevated ADAMTS4 was also observed by the immunostaining of lung samples from ARDS patients. The suppression of ADAMTS4 by siRNA in VECs ameliorated LPS-stimulated vascular permeability. The impairment of the cell surface expression of syndecan-1, a marker of the glycocalyx that is an extracellular matrix involved in vascular permeability, was dramatically inhibited by ADAMTS4 suppression. In addition, the suppression of ADAMTS4 protected against LPS-induced reductions in syndecan-1 and the adherens junction protein vascular endothelial cadherin. These results suggest that ADAMTS4 regulates VEC permeability in ARDS and may be a predictive marker and therapeutic target for ARDS.; 権利情報：© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).; identifier:International Journal of Molecular Sciences. 2023 Nov, vol.24, no.22, article no.16230; identifier:1661-6596; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4357; identifier:International Journal of Molecular Sciences, 24(22): 16230
• 国立国会図書館永続的識別子: info:ndljp/pid/13700893; https://dl.ndl.go.jp/pid/13700893
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2024-06-07T22:11:46+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 関連情報（URI）: https://doi.org/10.3390/ijms242216230
• 掲載誌（URI）: http://hdl.handle.net/10564/4357
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp