PXD057088

PXD057088 is an original dataset announced via ProteomeXchange.

Title	Enhanced Therapeutic Effects of Hypoxia-Preconditioned Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Renal Ischemic Injury
Description	Background Extracellular vesicles (EVs) secreted by mesenchymal stromal cells (MSCs) provide significant protection against renal ischemia-reperfusion injury (IRI). Hypoxia is considered an important method for enhancing the tissue repair capabilities of MSCs. However, the specific effects of hypoxia on MSCs and MSC-EVs, as well as their therapeutic potential for renal IRI, remain unclear. In this study, we investigated the alterations in MSCs and the production of MSC-EVs following hypoxia pre-treatment, and further explored the key intrinsic mechanisms by which hypoxic MSC-EVs treat renal IRI. Methods Human umbilical cord MSCs were cultured under normoxic and hypoxic conditions. Proliferation and related pathways were measured, and RNA sequencing was used to detect changes in the transcription profile. MSC-EVs from both normoxic and hypoxic conditions were isolated and characterized. In vivo, the localization and therapeutic effects of MSC-EVs were assessed in a rat renal IRI model. Histological examinations were employed to assess the structure, proliferation, and apoptosis of IRI kidney tissue respectively. Renal function was measured by analyzing serum creatinine and blood urea nitrogen levels. In vitro, the therapeutic potential of MSC-EVs were measured in renal tubular epithelial cells injured by antimycin A. Protein sequencing analysis of hypoxic MSC-EVs was conducted, and the depletion of Glutathione S-Transferase Omega 1 (GSTO1) in hypoxic MSC-EVs was performed to verify its key role in alleviating renal injury. Results Hypoxia alters MSCs transcription, promotes their proliferation, and increases the production of EVs. Hypoxia-pretreated MSC-EVs exhibited a superior ability to mitigate renal IRI, enhancing proliferation and reducing apoptosis of renal tubular epithelial cells both in vivo and in vitro. Protein profiling of the EVs revealed an accumulation of numerous anti-oxidative stress proteins, with GSTO1 being particularly prominent. GSTO1 knock down was significantly reduced the antioxidant and therapeutic effects in renal IRI of hypoxic MSC-EVs. Conclusions Hypoxia significantly promotes MSC-EVs generation and enhances the therapeutic effect of EVs on renal IRI. The effect of antioxidant stress induced by GSTO1 is one of the most important underlying mechanisms. Our findings underscore that hypoxia-pretreated MSC-EVs represent a novel and promising therapeutic intervention for renal IRI.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_03:59:32.120.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fei Yuan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	autoflex

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-23 00:31:14	ID requested
⏵ 1	2025-05-07 03:59:32	announced

Yuan F, Liu J, Zhong L, Liu P, Li T, Yang K, Gao W, Zhang G, Sun J, Zou X, Enhanced therapeutic effects of hypoxia-preconditioned mesenchymal stromal cell-derived extracellular vesicles in renal ischemic injury. Stem Cell Res Ther, 16(1):39(2025) [pubmed]

10.1186/s13287-025-04166-z;

submitter keyword: hypoxia pretreated, anti-oxidative stress, extracellular vesicles, mesenchymal stromal cells, renal ischemia reperfusion injury

Fei Yuan
contact affiliation	Shanghai Children Medical Center, School of Medicine, Shanghai Jiao Tong University
contact email	rounphy0723@163.com
lab head
Fei Yuan
contact affiliation	Shanghai Children Medical Center, School of Medicine, Shanghai Jiao Tong University
contact email	roundphy0723@163.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057088
     1. Label: PRIDE project
     2. Name: Enhanced Therapeutic Effects of Hypoxia-Preconditioned Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Renal Ischemic Injury