PXD055037-1

PXD055037 is an original dataset announced via ProteomeXchange.

Title	SAA1 delivered by tubular epithelial cell-derived extracellular vesicles aggravate sepsis-associated acute kidney injury by promoting NET formation
Description	Sepsis-associated acute kidney injury (SA-AKI) is highly lethal with a rapid onset, and effective drugs for treatment are lack due to the molecular pathogenesis underlying SA-AKI remains elusive. Tubular epithelial cells (TECs) have increasingly been recognized as a driving force in the progression of kidney diseases partly by releasing extracellular vesicles (EVs) carrying pro-inflammatory cargos. However, the role of TEC-derived EVs in the pathogenesis of SA-AKI remains unclear. This study demonstrated that EVs secreted from lipopolysaccharide (LPS)-stimulated TECs aggravated AKI through promoting neutrophil extracellular trap (NET) formation, which is an established feature of sepsis. Combined proteomics and scRNA-seq analysis, we found that LPS increased serum amyloid A1 (SAA1) expression in TECs and then released extracellularly through EVs. Further mechanistic study showed that SAA1 packaged in TEC-derived EVs was responsible for NET formation and AKI via activation of p38 MAPK signaling pathway in neutrophils. Specifically blocking EV secretion from TECs or inhibiting SAA1 upregulation in TECs by AAV9s reduced NET formation and alleviated LPS-induced AKI. Interestingly, modulating EVs release from TECs or SAA1 expression in TECs could also alleviate remote lung injury induced by LPS, suggesting that TEC-derived EVs are likely to play a role in deranged kidney-lung crosstalk during sepsis. More importantly, we identified that the expression level of SAA1 in plasma EVs combined plasma NETs may be promising prognostic indexes for SA-AKI patients. Here, we explored a new mode of TEC-neutrophil crosstalk mediated by EVs during SA-AKI and strategies to modify TEC-derived EVs and the cargo SAA1 could be a new avenue in developing therapeutics against SA-AKI.
HostingRepository	iProX
AnnounceDate	2024-08-22
AnnouncementXML	Submission_2025-12-31_00:04:15.916.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yang Jiao
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-21 22:14:34	ID requested
⏵ 1	2025-12-31 00:04:16	announced

Jiao Y, Liu M, Xie X, Pi M, Zhou L, Zhu W, Song J, Zhang T, Ma Z, Gu X, Tubular epithelial cell-derived extracellular vesicles carrying serum amyloid A1 exacerbate sepsis-associated acute kidney injury by promoting NETs formation. Front Immunol, 16():1654295(2025) [pubmed]

submitter keyword: Sepsis-associated acute kidney injury, Tubular epithelial cells, Extracellular vesicles, Neutrophil extracellular traps, Serum amyloid A1

Zhengliang Ma
contact affiliation	Department of Anesthesiology, Nanjing Drum Tower Hospital, The Affliated Hospital of Nanjing University Medical School, Nanjing, China
contact email	mazhengliang1964@nju.edu.cn
lab head
Yang Jiao
contact affiliation	Department of Anesthesiology, Nanjing Drum Tower Hospital, The Affliated Hospital of Nanjing University Medical School, Nanjing, China
contact email	15026967597@163.com
dataset submitter

iProX dataset URI