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Salvianolic acid B upregulates miR-744-5p expression in peripheral blood mononuclear cell–derived extracellular vesicles to alleviate uremic cardiomyopathy

ABSTRACT: Uremic cardiomyopathy (UCM) is a severe complication of uremia that lacks effective treatments. The role of immune dysfunction in hemodialysis patients with UCM remains unclear. Peripheral blood mononuclear cells (PBMCs) are major components of the immune system; however, they do not directly contact cardiomyocytes. In general, extracellular vesicles (EVs) function as intercellular communication mediators. Therefore, in this study, we first investigated the role of PBMC-derived EVs (PBMC-EVs) in UCM and identified EV-miR-744-5p as a key molecule involved in PBMC–cardiomyocyte communication. Mechanistically, indoxyl sulfate (IS) downregulated miR-744-5p expression in PBMC-EVs, leading to IGF2R upregulation in cardiomyocytes, thereby exacerbating myocardial injury via induction of hypertrophy, apoptosis, and inflammatory pathway activation in the cardiomyocytes. These files provide sequencing results on altered miRNAs in PBMC-EVs after IS stimulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE298327 | GEO | 2026/05/01

REPOSITORIES: GEO

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Project description:The role of extracellular vesicles (EVs), specifically exosomes, in intercellular communication likely plays a key role in placental orchestration of pregnancy and maternal immune sensing of the fetus. While murine models are powerful tools to study pregnancy and maternal-fetal immune interactions, in contrast to human placental exosomes, the content of murine placental and pregnancy exosomes remains largely understudied. Using a recently developed in vitro culture technique, murine trophoblast stem cells derived from B6 mice were differentiated into syncytial-like cells. EVs from the conditioned media, as well as from pregnant and non-pregnant sera, were enriched for exosomes. The RNA composition of these murine trophoblast-derived and pregnancy-associated exosome-enriched-EVs (ExoE-EVs) was determined using RNA-sequencing analysis and expression levels confirmed by qRT-PCR. Differentially abundant miRNAs were detected in syncytial differentiated ExoE-EVs, particularly from the X chromosome cluster (mmu-miR-322-3p, mmu-miR-322-5p, mmu-miR-503-5p, mmu-miR-542-3p, and mmu-miR-450a-5p). These were confirmed to be increased in pregnant mouse sera ExoE-EVs by qRT-PCR analysis. Interestingly, fifteen miRNAs were only present within the pregnancy-derived ExoE-EVs compared to non-pregnant controls. Mmu-miR-292-3p and mmu-miR-183-5p were noted to be some of the most abundant miRNAs in syncytial ExoE-EVs and were also present at higher levels in pregnant versus non-pregnant sera ExoE-EVs. The bioinformatics tool, MultiMir, was employed to query publicly available databases of predicted miRNA-target interactions. This analysis reveals that the X-chromosome miRNAs are predicted to target ubiquitin-mediated proteolysis and intracellular signaling pathways. Knowing the cargo of placental and pregnancy-specific ExoE-EVs as well as the predicted biological targets informs studies using murine models to examine not only maternal-fetal immune interactions but also the physiologic consequences of placental-maternal communication.

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Salvianolic acid B upregulates miR-744-5p expression in peripheral blood mononuclear cell–derived extracellular vesicles to alleviate uremic cardiomyopathy

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