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A Disintegrin and Metalloproteinase with Thrombospondin Motifs 4 Regulates Pulmonary Vascular Hyperpermeability through Destruction of Glycocalyx in Acute Respiratory Distress Syndrome

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...

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Autores principales: Konda, Makiko, Kitabatake, Masahiro, Ouji-Sageshima, Noriko, Tonomura, Rei, Furukawa, Ryutaro, Sonobe, Shota, Terada-Ikeda, Chiyoko, Takeda, Maiko, Kawaguchi, Masahiko, Ito, Toshihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671186/
https://www.ncbi.nlm.nih.gov/pubmed/38003418
http://dx.doi.org/10.3390/ijms242216230
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author Konda, Makiko
Kitabatake, Masahiro
Ouji-Sageshima, Noriko
Tonomura, Rei
Furukawa, Ryutaro
Sonobe, Shota
Terada-Ikeda, Chiyoko
Takeda, Maiko
Kawaguchi, Masahiko
Ito, Toshihiro
author_facet Konda, Makiko
Kitabatake, Masahiro
Ouji-Sageshima, Noriko
Tonomura, Rei
Furukawa, Ryutaro
Sonobe, Shota
Terada-Ikeda, Chiyoko
Takeda, Maiko
Kawaguchi, Masahiko
Ito, Toshihiro
author_sort Konda, Makiko
collection PubMed
description 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.
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spelling pubmed-106711862023-11-12 A Disintegrin and Metalloproteinase with Thrombospondin Motifs 4 Regulates Pulmonary Vascular Hyperpermeability through Destruction of Glycocalyx in Acute Respiratory Distress Syndrome Konda, Makiko Kitabatake, Masahiro Ouji-Sageshima, Noriko Tonomura, Rei Furukawa, Ryutaro Sonobe, Shota Terada-Ikeda, Chiyoko Takeda, Maiko Kawaguchi, Masahiko Ito, Toshihiro Int J Mol Sci Article 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. MDPI 2023-11-12 /pmc/articles/PMC10671186/ /pubmed/38003418 http://dx.doi.org/10.3390/ijms242216230 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Konda, Makiko
Kitabatake, Masahiro
Ouji-Sageshima, Noriko
Tonomura, Rei
Furukawa, Ryutaro
Sonobe, Shota
Terada-Ikeda, Chiyoko
Takeda, Maiko
Kawaguchi, Masahiko
Ito, Toshihiro
A Disintegrin and Metalloproteinase with Thrombospondin Motifs 4 Regulates Pulmonary Vascular Hyperpermeability through Destruction of Glycocalyx in Acute Respiratory Distress Syndrome
title A Disintegrin and Metalloproteinase with Thrombospondin Motifs 4 Regulates Pulmonary Vascular Hyperpermeability through Destruction of Glycocalyx in Acute Respiratory Distress Syndrome
title_full A Disintegrin and Metalloproteinase with Thrombospondin Motifs 4 Regulates Pulmonary Vascular Hyperpermeability through Destruction of Glycocalyx in Acute Respiratory Distress Syndrome
title_fullStr A Disintegrin and Metalloproteinase with Thrombospondin Motifs 4 Regulates Pulmonary Vascular Hyperpermeability through Destruction of Glycocalyx in Acute Respiratory Distress Syndrome
title_full_unstemmed A Disintegrin and Metalloproteinase with Thrombospondin Motifs 4 Regulates Pulmonary Vascular Hyperpermeability through Destruction of Glycocalyx in Acute Respiratory Distress Syndrome
title_short A Disintegrin and Metalloproteinase with Thrombospondin Motifs 4 Regulates Pulmonary Vascular Hyperpermeability through Destruction of Glycocalyx in Acute Respiratory Distress Syndrome
title_sort disintegrin and metalloproteinase with thrombospondin motifs 4 regulates pulmonary vascular hyperpermeability through destruction of glycocalyx in acute respiratory distress syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671186/
https://www.ncbi.nlm.nih.gov/pubmed/38003418
http://dx.doi.org/10.3390/ijms242216230
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