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Stromal-Interacting Molecule 1 (Stim1)/Orai1 Modulates Endothelial Permeability in Ventilator-Induced Lung Injury

BACKGROUND: Increased endothelial permeability is involved in ventilator-induced lung injury (VILI). Stim1/Orai1 mediates store-operated Ca(2+) activation, which modulates endothelial permeability. However, the underlying mechanisms of the Stim1/Orai1 pathway in VILI are poorly understood. MATERIAL/...

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Autores principales: Song, Xiumei, Liu, Yang, Dong, Ling, Wang, Yuelan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322368/
https://www.ncbi.nlm.nih.gov/pubmed/30589833
http://dx.doi.org/10.12659/MSM.911268
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author Song, Xiumei
Liu, Yang
Dong, Ling
Wang, Yuelan
author_facet Song, Xiumei
Liu, Yang
Dong, Ling
Wang, Yuelan
author_sort Song, Xiumei
collection PubMed
description BACKGROUND: Increased endothelial permeability is involved in ventilator-induced lung injury (VILI). Stim1/Orai1 mediates store-operated Ca(2+) activation, which modulates endothelial permeability. However, the underlying mechanisms of the Stim1/Orai1 pathway in VILI are poorly understood. MATERIAL/METHODS: Wistar rats were exposed to low tidal volume (7 mL/kg) or high tidal volume (40 mL/kg) ventilation. Human Lung Microvascular Endothelial Cells (HULEC) were subjected to 8% or 18% cyclic stretching (CS). BTP2 pretreatment was performed. Lung wet/dry weight ratio, histological changes of lung injury, and bronchoalveolar lavage fluid (BALF) protein were measured. Endothelial permeability and intracellular calcium concentration were evaluated in HULECs. Protein expression was determined by Western blotting. RESULTS: High tidal volume mechanical ventilation-induced lung injury (such as severe congestion and hemorrhage) and BTP2 pretreatment protected lungs from injury. The expression of Stim1, Orai1, and PKCα, lung wet/dry weight ratio, and BALF protein level significantly increased in the high tidal volume group compared to the control group and low tidal volume group. Importantly, BTP2 pretreatment alleviated the above-mentioned effects. Compared with exposure to 8% CS, the protein levels of Stim1, Orai1, and PKCα in HULECs significantly increased after exposure to 18% CS for 4 h, whereas BTP2 pretreatment significantly inhibited the increase (P<0.05). BTP2 pretreatment also suppressed increase of endothelial permeability and the intracellular calcium induced by 18% CS (P<0.05). CONCLUSIONS: When exposed to high tidal volume or large-magnitude CS, Stim1 and Orai1 expression are upregulated, which further activates calcium-sensitive PKCα and results in calcium overload, endothelial hyperpermeability, and, finally, lung injury.
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spelling pubmed-63223682019-01-25 Stromal-Interacting Molecule 1 (Stim1)/Orai1 Modulates Endothelial Permeability in Ventilator-Induced Lung Injury Song, Xiumei Liu, Yang Dong, Ling Wang, Yuelan Med Sci Monit Animal Study BACKGROUND: Increased endothelial permeability is involved in ventilator-induced lung injury (VILI). Stim1/Orai1 mediates store-operated Ca(2+) activation, which modulates endothelial permeability. However, the underlying mechanisms of the Stim1/Orai1 pathway in VILI are poorly understood. MATERIAL/METHODS: Wistar rats were exposed to low tidal volume (7 mL/kg) or high tidal volume (40 mL/kg) ventilation. Human Lung Microvascular Endothelial Cells (HULEC) were subjected to 8% or 18% cyclic stretching (CS). BTP2 pretreatment was performed. Lung wet/dry weight ratio, histological changes of lung injury, and bronchoalveolar lavage fluid (BALF) protein were measured. Endothelial permeability and intracellular calcium concentration were evaluated in HULECs. Protein expression was determined by Western blotting. RESULTS: High tidal volume mechanical ventilation-induced lung injury (such as severe congestion and hemorrhage) and BTP2 pretreatment protected lungs from injury. The expression of Stim1, Orai1, and PKCα, lung wet/dry weight ratio, and BALF protein level significantly increased in the high tidal volume group compared to the control group and low tidal volume group. Importantly, BTP2 pretreatment alleviated the above-mentioned effects. Compared with exposure to 8% CS, the protein levels of Stim1, Orai1, and PKCα in HULECs significantly increased after exposure to 18% CS for 4 h, whereas BTP2 pretreatment significantly inhibited the increase (P<0.05). BTP2 pretreatment also suppressed increase of endothelial permeability and the intracellular calcium induced by 18% CS (P<0.05). CONCLUSIONS: When exposed to high tidal volume or large-magnitude CS, Stim1 and Orai1 expression are upregulated, which further activates calcium-sensitive PKCα and results in calcium overload, endothelial hyperpermeability, and, finally, lung injury. International Scientific Literature, Inc. 2018-12-27 /pmc/articles/PMC6322368/ /pubmed/30589833 http://dx.doi.org/10.12659/MSM.911268 Text en © Med Sci Monit, 2018 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Animal Study
Song, Xiumei
Liu, Yang
Dong, Ling
Wang, Yuelan
Stromal-Interacting Molecule 1 (Stim1)/Orai1 Modulates Endothelial Permeability in Ventilator-Induced Lung Injury
title Stromal-Interacting Molecule 1 (Stim1)/Orai1 Modulates Endothelial Permeability in Ventilator-Induced Lung Injury
title_full Stromal-Interacting Molecule 1 (Stim1)/Orai1 Modulates Endothelial Permeability in Ventilator-Induced Lung Injury
title_fullStr Stromal-Interacting Molecule 1 (Stim1)/Orai1 Modulates Endothelial Permeability in Ventilator-Induced Lung Injury
title_full_unstemmed Stromal-Interacting Molecule 1 (Stim1)/Orai1 Modulates Endothelial Permeability in Ventilator-Induced Lung Injury
title_short Stromal-Interacting Molecule 1 (Stim1)/Orai1 Modulates Endothelial Permeability in Ventilator-Induced Lung Injury
title_sort stromal-interacting molecule 1 (stim1)/orai1 modulates endothelial permeability in ventilator-induced lung injury
topic Animal Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322368/
https://www.ncbi.nlm.nih.gov/pubmed/30589833
http://dx.doi.org/10.12659/MSM.911268
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