Platelet-derived extracellular vesicles aggravate septic acute via ARF6

被引:7
|
作者
Lu, Xun [1 ,2 ]
Jiang, Guiya [1 ,2 ]
Gao, Yue [1 ,2 ]
Chen, Qi [3 ]
Sun, Si [1 ,2 ]
Mao, Weipu [1 ,2 ]
Zhang, Nieke [1 ,2 ]
Zhu, Zepeng [1 ,2 ]
Wang, Dong [1 ,2 ]
Zhang, Guangyuan [1 ,2 ]
Chen, Ming [1 ,2 ]
Zhang, Lei [1 ,2 ]
Chen, Shuqiu [1 ,2 ]
机构
[1] Southeast Univ, Affiliated Zhongda Hosp, Dept Urol, Nanjing, Peoples R China
[2] Southeast Univ, Inst Urol, Surg Res Ctr, Sch Med, Nanjing, Peoples R China
[3] Southeast Univ, Affiliated Zhongda Hosp, Dept Intervent Radiol & Vasc Surg, Nanjing, Peoples R China
来源
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2023年 / 19卷 / 16期
基金
中国国家自然科学基金;
关键词
sepsis; extracellular vesicles; platelet; acute kidney injury; ARF6; ACUTE KIDNEY INJURY; SEPSIS; INFLAMMATION; ACTIVATION; MICROPARTICLES; DYSFUNCTION; MECHANISMS; GENERATION; INHIBITION; EXOSOMES;
D O I
10.7150/ijbs.87165
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Circulating plasma extracellular vesicles (EVs) mostly originate from platelets and may promote organ dysfunction in sepsis. However, the role of platelet-derived EVs in sepsis-induced acute kidney injury (AKI) remains poorly understood. The present study extracted EVs from the supernatant of human platelets treated with phosphate buffer saline (PBS) or lipopolysaccharide (LPS). Then, we subjected PBS-EVs or LPS-EVs to cecal ligation and puncture (CLP) mice in vivo or LPS-stimulated renal tubular epithelial cells (RTECs) in vitro. Our results indicated that LPS-EVs aggravate septic AKI via promoting apoptosis, inflammation and oxidative stress. Further, ADP-ribosylation factor 6 (ARF6) was identified as a differential protein between PBS-EVs and LPS-EVs by quantitative proteomics analysis. Mechanistically, ARF6 activated ERK/Smad3/p53 signaling to exacerbate sepsis-induced AKI. LPS upregulated ARF6 in RTECs was dependent on TLR4/MyD88 pathway. Both genetically and pharmacologically inhibition of ARF6 attenuated septic AKI. Moreover, platelets were activated by TLR4 and its downstream mediator IKK controlled platelet secretion during sepsis. Inhibition of platelet secretion alleviated septic AKI. Collectively, our study demonstrated that platelet-derived EVs may be a therapeutic target in septic AKI.
引用
收藏
页码:5055 / 5073
页数:19
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