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

• Material Type: 博士論文
• Title: A disintegrin and metalloproteinase with thrombospondin motifs 4 regulates pulmonary vascular hyperpermeability through destruction of glycocalyx in acute respiratory distress syndrome
• Author/Editor: Konda, Makiko; Kitabatake, Masahiro; Ouji-Sageshima, Noriko; Tonomura, Rei; Furukawa, Ryutaro; Sonobe, Shota; Terada-Ikeda, Chiyoko; Takeda, Maiko; Kawaguchi, Masahiko; Ito, Toshihiro
• Author Heading: Konda, Makiko; Kitabatake, Masahiro; Ouji-Sageshima, Noriko; Tonomura, Rei; Furukawa, Ryutaro; Sonobe, Shota; Terada-Ikeda, Chiyoko; Takeda, Maiko; Kawaguchi, Masahiko; Ito, Toshihiro
• Publication, Distribution, etc.: MDPI
• Publication Date: 2023-11
• Publication Date (W3CDTF): 2023-11
• Alternative Title: 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
• Periodical title: International Journal of Molecular Sciences
• No. or year of volume/issue: 24 22
• Volume: 24
• Issue: 22
• Pages: 16230-
• ISSN (Periodical Title): ISSN : 1661-6596
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2024-03-14
• Dissertation Number: 甲第906号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: ADAMTS4; ARDS; endothelial cells; glycocalyx; vascular permeability
• Target Audience: 一般
• Note (General): 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
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4357/1/01%e7%94%b2906%e6%9c%ac%e6%96%87.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4357/2/02%e7%94%b2906%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4357/3/03%e7%94%b2906%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.3390/ijms242216230
• 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