Mechanical Stress Induced NOX2 Promotes Endothelial Dysfunction in Ventilator‐Induced Lung Injury: Potential Treatment with Quercetin
Abstract Mechanical ventilation (MV) is a treatment that helps people who are unable to breathe on their own. However, the use of MV leads to the development of ventilator‐induced lung injury (VILI). Here, it is found that VILI with endothelial barrier disruption is accompanied by elevated reactive...
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Wiley
2025-07-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202502639 |
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| author | Tao Jiang Yabing Zhang Zhiye Guo He Ren Weiyi Hu Qingping Yao Yunlong Huo Yingxin Qi Kai Huang |
| author_facet | Tao Jiang Yabing Zhang Zhiye Guo He Ren Weiyi Hu Qingping Yao Yunlong Huo Yingxin Qi Kai Huang |
| author_sort | Tao Jiang |
| collection | DOAJ |
| description | Abstract Mechanical ventilation (MV) is a treatment that helps people who are unable to breathe on their own. However, the use of MV leads to the development of ventilator‐induced lung injury (VILI). Here, it is found that VILI with endothelial barrier disruption is accompanied by elevated reactive oxygen species (ROS) in mice. NADPH oxidase 2 (NOX2, also known as CYBB or gp91phox) is first examined to be the main source of ROS to repress endothelial junction. Besides, 20%‐0.5 Hz high cyclic stretch (high CS) significantly increases NOX2 expression and inhibits endothelial junction protein expression. NOX2 activates the downstream Calcium–calmodulin (CaM)‐dependent protein kinase II (CaMKII)/ Extracellular signal‐regulated protein kinase 1/2 (ERK1/2) signaling pathway through the regulation of ROS. This pathway is confirmed by high MV stimulation in vivo and high CS in vitro. Of note, quercetin, as an antioxidant, is effective in preventing mechanical stretch‐induced endothelial dysfunction by scavenging ROS. Omics data indicated that there is a similar gene expression pattern in cecal ligation and puncture (CLP) and VILI. Pre‐administration of quercetin significantly improves the survival rate of mice via inactivating ROS/CaMKII/ERK1/2 axis. Quercetin pre‐treatment not only preventes MV‐induced lung injury but also attenuates existing inflammation‐induced lung injury. |
| format | Article |
| id | doaj-art-93c46c650f094a8a8634e8a5cfaedd81 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-93c46c650f094a8a8634e8a5cfaedd812025-08-20T02:50:52ZengWileyAdvanced Science2198-38442025-07-011228n/an/a10.1002/advs.202502639Mechanical Stress Induced NOX2 Promotes Endothelial Dysfunction in Ventilator‐Induced Lung Injury: Potential Treatment with QuercetinTao Jiang0Yabing Zhang1Zhiye Guo2He Ren3Weiyi Hu4Qingping Yao5Yunlong Huo6Yingxin Qi7Kai Huang8Institute of Mechanobiology & Medical Engineering School of Life Sciences & Biotechnology Shanghai Jiao Tong University 800 Dongchuan Road, Minhang Shanghai 200240 ChinaDepartment of Anesthesiology West China Second University Hospital Sichuan University Chengdu 610041 ChinaInstitute of Mechanobiology & Medical Engineering School of Life Sciences & Biotechnology Shanghai Jiao Tong University 800 Dongchuan Road, Minhang Shanghai 200240 ChinaInstitute of Mechanobiology & Medical Engineering School of Life Sciences & Biotechnology Shanghai Jiao Tong University 800 Dongchuan Road, Minhang Shanghai 200240 ChinaInstitute of Mechanobiology & Medical Engineering School of Life Sciences & Biotechnology Shanghai Jiao Tong University 800 Dongchuan Road, Minhang Shanghai 200240 ChinaInstitute of Mechanobiology & Medical Engineering School of Life Sciences & Biotechnology Shanghai Jiao Tong University 800 Dongchuan Road, Minhang Shanghai 200240 ChinaInstitute of Mechanobiology & Medical Engineering School of Life Sciences & Biotechnology Shanghai Jiao Tong University 800 Dongchuan Road, Minhang Shanghai 200240 ChinaInstitute of Mechanobiology & Medical Engineering School of Life Sciences & Biotechnology Shanghai Jiao Tong University 800 Dongchuan Road, Minhang Shanghai 200240 ChinaInstitute of Mechanobiology & Medical Engineering School of Life Sciences & Biotechnology Shanghai Jiao Tong University 800 Dongchuan Road, Minhang Shanghai 200240 ChinaAbstract Mechanical ventilation (MV) is a treatment that helps people who are unable to breathe on their own. However, the use of MV leads to the development of ventilator‐induced lung injury (VILI). Here, it is found that VILI with endothelial barrier disruption is accompanied by elevated reactive oxygen species (ROS) in mice. NADPH oxidase 2 (NOX2, also known as CYBB or gp91phox) is first examined to be the main source of ROS to repress endothelial junction. Besides, 20%‐0.5 Hz high cyclic stretch (high CS) significantly increases NOX2 expression and inhibits endothelial junction protein expression. NOX2 activates the downstream Calcium–calmodulin (CaM)‐dependent protein kinase II (CaMKII)/ Extracellular signal‐regulated protein kinase 1/2 (ERK1/2) signaling pathway through the regulation of ROS. This pathway is confirmed by high MV stimulation in vivo and high CS in vitro. Of note, quercetin, as an antioxidant, is effective in preventing mechanical stretch‐induced endothelial dysfunction by scavenging ROS. Omics data indicated that there is a similar gene expression pattern in cecal ligation and puncture (CLP) and VILI. Pre‐administration of quercetin significantly improves the survival rate of mice via inactivating ROS/CaMKII/ERK1/2 axis. Quercetin pre‐treatment not only preventes MV‐induced lung injury but also attenuates existing inflammation‐induced lung injury.https://doi.org/10.1002/advs.202502639endothelial barrier dysfunctionendothelial cells (ECs)mechanical stressmechanotransductionNADPH oxidase (NOX)quercetin |
| spellingShingle | Tao Jiang Yabing Zhang Zhiye Guo He Ren Weiyi Hu Qingping Yao Yunlong Huo Yingxin Qi Kai Huang Mechanical Stress Induced NOX2 Promotes Endothelial Dysfunction in Ventilator‐Induced Lung Injury: Potential Treatment with Quercetin Advanced Science endothelial barrier dysfunction endothelial cells (ECs) mechanical stress mechanotransduction NADPH oxidase (NOX) quercetin |
| title | Mechanical Stress Induced NOX2 Promotes Endothelial Dysfunction in Ventilator‐Induced Lung Injury: Potential Treatment with Quercetin |
| title_full | Mechanical Stress Induced NOX2 Promotes Endothelial Dysfunction in Ventilator‐Induced Lung Injury: Potential Treatment with Quercetin |
| title_fullStr | Mechanical Stress Induced NOX2 Promotes Endothelial Dysfunction in Ventilator‐Induced Lung Injury: Potential Treatment with Quercetin |
| title_full_unstemmed | Mechanical Stress Induced NOX2 Promotes Endothelial Dysfunction in Ventilator‐Induced Lung Injury: Potential Treatment with Quercetin |
| title_short | Mechanical Stress Induced NOX2 Promotes Endothelial Dysfunction in Ventilator‐Induced Lung Injury: Potential Treatment with Quercetin |
| title_sort | mechanical stress induced nox2 promotes endothelial dysfunction in ventilator induced lung injury potential treatment with quercetin |
| topic | endothelial barrier dysfunction endothelial cells (ECs) mechanical stress mechanotransduction NADPH oxidase (NOX) quercetin |
| url | https://doi.org/10.1002/advs.202502639 |
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