氧化应激
炎症
脂磷壁酸
分子生物学
线粒体
金黄色葡萄球菌
化学
医学
免疫学
生物
生物化学
细菌
遗传学
作者
Si‐Hao Jin,Jiejie Sun,Gang Liu,Li Shen,Yuan Weng,Jinyou Li,Min Chen,Ying‐Ying Wang,Zhiqi Gao,Feng Jiang,Sheng‐Peng Li,Dan Chen,Qingfeng Pang,Yingwei Wu,Zhi‐Qiang Wang
出处
期刊:MedComm
[Wiley]
日期:2023-12-01
卷期号:4 (6)
摘要
Staphylococcus aureus (SA) is a major cause of sepsis, leading to acute lung injury (ALI) characterized by inflammation and oxidative stress. However, the role of the Nrf2/PHB2 pathway in SA-induced ALI (SA-ALI) remains unclear. In this study, serum samples were collected from SA-sepsis patients, and a SA-ALI mouse model was established by grouping WT and Nrf2-/- mice after 6 h of intraperitoneal injection. A cell model simulating SA-ALI was developed using lipoteichoic acid (LTA) treatment. The results showed reduced serum Nrf2 levels in SA-sepsis patients, negatively correlated with the severity of ALI. In SA-ALI mice, downregulation of Nrf2 impaired mitochondrial function and exacerbated inflammation-induced ALI. Moreover, PHB2 translocation from mitochondria to the cytoplasm was observed in SA-ALI. The p-Nrf2/total-Nrf2 ratio increased in A549 cells with LTA concentration and treatment duration. Nrf2 overexpression in LTA-treated A549 cells elevated PHB2 content on the inner mitochondrial membrane, preserving genomic integrity, reducing oxidative stress, and inhibiting excessive mitochondrial division. Bioinformatic analysis and dual-luciferase reporter assay confirmed direct binding of Nrf2 to the PHB2 promoter, resulting in increased PHB2 expression. In conclusion, Nrf2 plays a role in alleviating SA-ALI by directly regulating PHB2 transcription and maintaining mitochondrial function in lung cells.
科研通智能强力驱动
Strongly Powered by AbleSci AI