Dataset Information

The cargos and roles of small extracellular vesicles from cochlear explants in cisplatin-induced ototoxicity

ABSTRACT: Small extracellular vesicles (sEVs) play an important role in intercellular communication as well as pathological development. Here, to explore the roles of sEVs in the progression of cisplatin-induced ototoxicity, we isolated sEVs from the conditioned culture medium of cisplatin-induced cochlear explants (Cis-sEVs) and the control group (Ctrl-sEVs) and profiled their cargos using label-free LC-MS/MS. Numerous proteins involved in the regulation of the damage response were enriched in the Cis-sEVs. Cltc, Cct2, and Hspa8, which are potentially involved in protein homeostasis and autophagy, are up-regulated in Cis-sEVs compared to Ctrl-sEVs but not in cisplatin-damaged cochlear tissue or in HEI-OC1 cell lysates.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cochlea

SUBMITTER: Jingru Ai

LAB HEAD: Renjie Chai

PROVIDER: PXD052123 | Pride | 2025-09-01

REPOSITORIES: Pride

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Publications

Small Extracellular Vesicles Orchestrate Cisplatin-Induced Ototoxicity: Potential Biomarker and Targets Discovery.

Ai Jingru J Zhang Shasha S Dai Mingchen M Jiang Pei P Huang Jingyuan J Xiao Hairong H Lin Yanqin Y Tang Xujun X Tong Wei W He Jun J Mao Qiuyue Q Wang Yintao Y Ye Zixuan Z Wang Tian T Chai Renjie R

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20250524 30

Cisplatin-induced ototoxicity remains a clinical dilemma with limited mechanistic understanding and no food and drug administration (FDA)-approved therapies. Despite emerging roles of small extracellular vesicles (sEV) in drug ototoxicity, their molecular cargo profiles and causal roles to cisplatin-induced ototoxicity are unexplored. This study systematically investigates sEV derived from cochlear explants treated with cisplatin (Cis-sEV) and controls (Ctrl-sEV) using multi-omics profiling. Thr ...[more]

PMID: 40411396

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Project description:Recent studies have described a new mechanism of intercellular communication mediated by various types of extracellular vesicles (EVs). In particular, exosomes are small EVs (sEVs) released to the extracellular environment by the fusion of the endosomal pathway-related multivesicular bodies (containing intraluminal vesicles) with the plasma membrane. sEVs contain a molecular cargo consisting of lipids, proteins, and nucleic acids. However, the loading mechanisms for this complex molecular cargo have not yet been completely elucidated. In that line, the post translational modification SUMO (Small Ubiquitin-like Modifier) has been shown to impact the incorporation of select proteins into sEVs. We therefore decided to investigate whether SUMOylation is a mechanism that defines protein loading to sEVs. In order to investigate the role of SUMOylation in cargo loading into sEVs, we utilized astrocytes, an essential cell type of the central nervous system with homeostatic functions, to study the impact of SUMOylation on the protein cargo of sEVs. Following SUMO overexpression, achieved by transfection of SUMO plasmids or experimental conditions that modulate SUMOylation in primary astrocyte cultures, we detected proteins related to cell division, translation, and transcription by mass-spectrometry. In astrocyte cultures treated with the general SUMOylation inhibitor 2-D08 (2′,3′,4′-trihydroxy-flavone, 2-(2,3,4-Trihydroxyphenyl)-4H-1-Benzopyran-4-one) we observed an increase in the number of sEVs and a decreased amount of protein cargo within them. In turn, in astrocytes treated with the stress hormone corticosterone, we found an increase of SUMO-2 conjugated proteins and sEVs from these cells contained an augmented protein cargo. In this case, the proteins detected with mass-spectrometry were mostly proteins related to protein translation. To test whether astrocyte-derived sEVs obtained in these experimental conditions could modulate protein synthesis in target cells, we incubated primary neurons with astrocyte-derived sEVs. sEVs from corticosterone-treated astrocytes stimulated protein synthesis while no difference was found with sEVs derived from 2-D08-treated astrocytes. Our results show that SUMO conjugation plays a fundamental role in defining the protein cargo of sEVs impacting the physiological function of target cells.

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	22P18340001_1.raw	Raw
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	22P18340001_3.mgf	Mgf