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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1544610
This article is part of the Research Topic Targeting Pulmonary Endothelium in Acute Lung Injury and Acute Respiratory Distress Syndrome View all 6 articles
CMTM3 Regulates Vascular Endothelial Cell Dysfunction by Influencing Pulmonary Vascular Endothelial Permeability and Inflammation in ARDS
Provisionally accepted- Peking University People's Hospital, Beijing, China
CMTM3 is a member of the human chemokine-like factor superfamily. The mechanistic role of 15 CMTM3 in acute respiratory distress syndrome (ARDS) is not known. This study investigated the 16 role of CMTM3 in the progression of ARDS and its impact on the function of vascular endothelial 17 cells. ARDS modeling in human umbilical vascular endothelial cells (HUVECs) was performed by 18 treating with lipopolysaccharide (LPS) or hypoxia/reoxygenation. We assessed CMTM3 expression 19 levels in the LPS- and hypoxia/reoxygenation-stimulated HUVEC cells. Furthermore, we assessed 20 the role of CMTM3 in the permeability function and inflammatory response of the vascular 21 endothelial cells under ARDS conditions using HUVEC cells with CMTM3 22 overexpression(adCMTM3) or knockdown(shCMTM3). Concurrently, we generated CMTM3 23 knockout (CMTM3ko) mice and evaluated the differences in pulmonary vascular permeability, 24 inflammatory lung injury, and survival rates between the CMTM3ko-ARDS and WT-ARDS model 25 mice. HUVECs stimulated with LPS and hypoxia/reoxygenation showed significantly higher 26 CMTM3 expression compared to the control group (p<0.05). Compared with the adsham-HUVECs, 27 adCMTM3-HUVECs stimulated with LPS and hypoxia/reoxygenation demonstrated significantly 28 higher cellular permeability (p<0.05) as well as IL-6 and TNF-α expression levels (p<0.05). 29 Conversely, shCMTM3-HUVECs stimulated with LPS and hypoxia/reoxygenation showed 30 significantly reduced cellular permeability as well as IL-6 and TNF-α expression levels (p<0.05). In 31This is a provisional file, not the final typeset article 2vivo ARDS modeling experiments demonstrated that CMTM3-knockout ARDS mice exhibited 32 significantly higher survival rates (p=0.0194) as well as significantly reduced lung injury and 33 pulmonary vascular permeability (p<0.05) compared to the wild-type ARDS mice. These findings 34 demonstrated that CMTM3 played a critical role in the development of ARDS by influencing 35 permeability of the pulmonary vascular endothelial cells and lung inflammation. Therefore, CMTM3 36 is a potential therapeutic target in ARDS.
Keywords: ARDS, HUVECs, CMTM3, Inflammation, Immunosuppression
Received: 13 Dec 2024; Accepted: 05 Mar 2025.
Copyright: © 2025 Ziyan, Gang, Xue, Lihe, Zhao, Li, Chun, Zhengzhou and Fengxue. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhu Fengxue, Peking University People's Hospital, Beijing, China
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