Work

Bone Marrow Mesenchymal Stem Cell‐Derived Exosomal USP10 Alleviates Cerebral Ischemia‐Reperfusion Injury via Stabilizing SLC7A11 by Deubiquitination

Year: 2025

Type: article

Abstract: ABSTRACT Ubiquitination is a widespread posttranslational modification that plays an important biological regulatory role in cells. Research has reported that bone marrow mesenchymal stem cells (BMSCs) can inhibit cerebral ischemia‐reperfusion injury. This study aims to explore the effect of deubiquitinating enzymes ubiquitin‐specific peptidase 10 (USP10) modified BMSCs exosomes on cerebral ischemia‐reperfusion injury and the underlying mechanism. PC12 cells were stimulated with oxygen–glucose deprivation/reoxygenation (OGD/R). The gene expression was detected by qRT‐PCR and western blots. CCK8, EdU, and flow cytometry assays were conducted to assess cell viability, proliferation, and apoptosis, respectively. Fe 2+ , ROS, and GSH levels were detected to evaluate ferroptosis. Moreover, BMSCs were identified by flow cytometry, and exosomes were identified by transmission electron microscopy. The relationship between USP10 and solute carrier family 7 member 11 (SLC7A11) was confirmed by immunoprecipitation assay. In addition, the rat cerebral infarction model was conducted to explore the role of USP10‐modified BMSCs exosomes in vivo. Overexpression of USP10 alleviated OGD/R‐induced PC12 cell injury and ferroptosis. BMSCs exosomes could transport USP10, and USP10‐modified BMSCs exosomes mitigated OGD/R‐induced injury in PC12 cells. Besides, USP10 regulated SLC7A11 protein expression by mediating its deubiquitination. SLC7A11 knockdown restored the effects of USP10‐modified BMSCs exosomes on OGD/R‐induced PC12 cells. Moreover, USP10‐modified BMSCs exosomes repressed cerebral infarction and ferroptosis in vivo. USP10‐modified BMSCs exosomes protected against cerebral ischemia‐reperfusion injury via mediating the deubiquitination of SLC7A11.

Source: Journal of Biochemical and Molecular Toxicology

DOI: 10.1002/jbt.70246

Authors: Nannuan Liu, Yue Xu, Genshan Gao, Yao Liu, Wenli Hu

Institutions: Hubei University of Medicine, Capital Medical University, Beijing Chao-Yang Hospital, Capital Medical University

Language: English

Topic: Extracellular vesicles in disease

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

OpenAlex ID: W4409219759

FWCI: 1.26

Cites: 38

Cited by: 5

Related to: 10