PXD070332

PXD070332 is an original dataset announced via ProteomeXchange.

Title	mitoEVs from renal tubular epithelial cells promote remote lung injury by targeting endothelial cells via mtDNA-cGAS/STING axis during sepsis
Description	Sepsis is a life threatening systemic inflammatory response syndrome, often leading to multiple organ dysfunction syndrome (MODS). However, whether interorgan crosstalk exist between kidney and lung during sepsis, and the mechanisms and mediators are not well understood. In this study, we provide the first conclusive evidence that the kidney-derived extracellular vesicles (EVs) are involved in remote lung injury during sepsis. Using proteomics analysis, we demonstrated that sepsis triggered the formation of mitochondrial-derived vesicles (MDVs) by upregulating sorting nexin 9 (SNX9) in renal tubular epithelial cells (TECs), released extracellular as mitochondria-rich EVs (mitoEVs), and then entered circulation. Next, using in vivo EVs administration and target inhibition of EVs releasing from renal TECs in a septic model, we define an axis through which renal TECs-derived mitoEVs mediated remote lung injury during sepsis. Further single-cell RNA sequencing analysis revealed that renal TECs-derived mitoEVs targeted lung endothelial cells, shifted endothelial cells to a proinflammatory phenotype, impaired endothelial integrity and promoted immune cell accumulation. Mechanistically, renal TECs-derived mitoEVs activated the cGAS-STING pathway in lung endothelial cells by transferring mitochondrial DNA (mtDNA), and ZBP1 served as a cooperative partner for cGAS-STING pathway activation. Additionally, early detection of plasma mitoEVs provides a valuable biomarker for identifying acute respiratory distress syndrome (ARDS) and predicting the mortality as well. These findings advance our understanding of EVs-facilitated interorgan communication during sepsis-related MODS and further suggest potential therapeutic strategies targeting SNX9/MDVs (kidney)-mitoEVs (circulation)-mtDNA/cGAS/STING (lung) axis to alleviate sepsis-related ARDS.
HostingRepository	iProX
AnnounceDate	2025-11-05
AnnouncementXML	Submission_2025-11-04_17:59:54.019.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yang Jiao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-04 17:59:05	ID requested
⏵ 1	2025-11-04 17:59:54	announced

Dataset with its publication pending

submitter keyword: kidney‒lung crosstalk, mitochondria-rich EVs, mitochondrial-derived vesicles, sorting nexin 9, lung endothelial cells, mtDNA, cGAS-STING

Zhengliang Ma
contact affiliation	Nanjing Drum Tower Hospital
contact email	mazhengliang1964@nju.edu.cn
lab head
Yang Jiao
contact affiliation	Nanjing Drum Tower Hospital
contact email	15026967597@163.com
dataset submitter

iProX dataset URI