التفاصيل البيبلوغرافية
العنوان: |
S1PR3 inhibition protects against LPS-induced ARDS by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation |
المؤلفون: |
Junnan Peng, Rui Tang, Jing He, Qian Yu, Daoxin Wang, Di Qi |
المصدر: |
Journal of Translational Medicine, Vol 22, Iss 1, Pp 1-26 (2024) |
بيانات النشر: |
BMC, 2024. |
سنة النشر: |
2024 |
المجموعة: |
LCC:Medicine |
مصطلحات موضوعية: |
S1PR3, ARDS, NF-κB, Mitochondrial oxidative phosphorylation, Endothelial cell, Medicine |
الوصف: |
Abstract Background Inflammation and endothelial barrier dysfunction are the major pathophysiological changes in acute respiratory distress syndrome (ARDS). Sphingosine-1-phosphate receptor 3 (S1PR3), a G protein-coupled receptor, has been found to mediate inflammation and endothelial cell (EC) integrity. However, the function of S1PR3 in ARDS has not been fully elucidated. Methods We used a murine lipopolysaccharide (LPS)-induced ARDS model and an LPS- stimulated ECs model to investigate the role of S1PR3 in anti-inflammatory effects and endothelial barrier protection during ARDS. Results We found that S1PR3 expression was increased in the lung tissues of mice with LPS-induced ARDS. TY-52156, a selective S1PR3 inhibitor, effectively attenuated LPS-induced inflammation by suppressing the expression of proinflammatory cytokines and restored the endothelial barrier by repairing adherens junctions and reducing vascular leakage. S1PR3 inhibition was achieved by an adeno-associated virus in vivo and a small interfering RNA in vitro. Both the in vivo and in vitro studies demonstrated that pharmacological or genetic inhibition of S1PR3 protected against ARDS by inhibiting the NF-κB pathway and improving mitochondrial oxidative phosphorylation. Conclusions S1PR3 inhibition protects against LPS-induced ARDS via suppression of pulmonary inflammation and promotion of the endothelial barrier by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation, indicating that S1PR3 is a potential therapeutic target for ARDS. |
نوع الوثيقة: |
article |
وصف الملف: |
electronic resource |
اللغة: |
English |
تدمد: |
1479-5876 |
Relation: |
https://doaj.org/toc/1479-5876 |
DOI: |
10.1186/s12967-024-05220-9 |
URL الوصول: |
https://doaj.org/article/32ffabffc0994b17887acc9802ed5d2f |
رقم الانضمام: |
edsdoj.32ffabffc0994b17887acc9802ed5d2f |
قاعدة البيانات: |
Directory of Open Access Journals |