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Protective role of miR-712-3p in heatstroke-induced brain injury: involvement of neuronal lysosomal function and association with astrocytic exosome-enriched preparations.

Overview

Authors: Yahong Chen1,2,3, Jie Zhu1,4, Shuhuan Li3, Peishan Liang1,5, Yiqiong Zhang1,5, Guangli Ren1,2,5
  1. Department of Pediatric, General Hospital of Southern Theater Command, Guangzhou, China
  2. The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
  3. Department of Pediatric, The Eighth Affiliated Hospital of Southern Medical University (The First People’s Hospital of Shunde Foshan), Foshan, China
  4. Department of Pediatric, Daping Hospital, Army Medical University, Chongqing, China
  5. Guangzhou University of Chinese Medicine, Guangzhou, China
Journal: Frontiers in pharmacology, volume 17, article 1718110
Dates: received 3 October 2025; accepted 3 March 2026; published online 15 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.3389/fphar.2026.1718110 · PMID 42064819 · PMCID PMC13125176 · OpenAlex W7154530926
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: cellular / molecular (subfield)
Methods: Statistics
Keywords: astrocyte, brain injury, exosome-enriched preparations, heatstroke, miR-712-3p
Topic: Extracellular vesicles in disease (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Citations: not cited yet (Europe PMC); 43 references in the paper

Abstract

While glia-derived exosomes have been extensively studied in heatstroke induced brain injury, the role of exosomal microRNAs (miRNAs) secreted by astrocyte remains underexplored. In this study, the viability of C8-D1A cells decreased after heat stress, apoptosis rate and the expression levels of proinflammatory cytokines such as TNF-α, IL-6, IL-1α and IL-1β increased to different degrees. The extracellular vesicles obtained by ultracentrifugation were identified via transmission electron microscopy (TEM), nanoparticle tracking technology Nanoparticle tracking analysis, and nanoflow cytometry (nanoFCM), which was consistent with the characterization of the exosomes. In the following sections, the collected EVs will be referred to as exosome-enriched preparations. Exosome-enriched preparations’s miRNA sequencing identified 23 differentially expressed miRNAs. Further functional analysis via gene ontology enrichment revealed that 46 genes regulated cell death and that 38 genes were involved in neuronal apoptosis. Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis revealed that the main enriched signalling pathways were involved in biological processes such as apoptosis, inflammation, and oxidative stress. Among them, miR-712-3p was the most upregulated miRNA in the heat stress group. MiR-712-3p was overexpressed and inhibited by intranasal administration in vivo and cell transfection in vitro, and it was found that miR-712-3p could reduce brain injury and improve neuronal activity under heat stress. Moreover, RNA sequencing of neurons and transmission electron microscopy revealed that miR-712-3p can affect lysosomal function. Differential expressed genes can be involved in specific lysosome-related processes, and we predicted Atp6v1c1 associated with miR-712-3p as a candidate gene through the miRDB database. Collectively, our findings demonstrate that miR-712-3p ameliorates heat stroke-induced brain injury, with this protective effect being linked to the modulation of neuronal lysosomal function. Furthermore, the study confirms the involvement of astrocyte-derived exosome-enriched preparations in mediating this protective effect in vitro.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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Data availability statement

The data presented in the study are deposited in the GEO repository, accession numbers GSE327014 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327014) and GSE327120.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 6 authors, 5 keywords, 43 references.

Cite

This paper

Chen, Y., Zhu, J., Li, S., Liang, P., Zhang, Y., & Ren, G. (2026). Protective role of miR-712-3p in heatstroke-induced brain injury: involvement of neuronal lysosomal function and association with astrocytic exosome-enriched preparations. Frontiers in pharmacology, 17, 1718110. https://doi.org/10.3389/fphar.2026.1718110

BibTeX

@article{chen2026protective,
author = {Chen, Yahong and Zhu, Jie and Li, Shuhuan and Liang, Peishan and Zhang, Yiqiong and Ren, Guangli},
title = {{Protective role of miR-712-3p in heatstroke-induced brain injury: involvement of neuronal lysosomal function and association with astrocytic exosome-enriched preparations}},
journal = {Frontiers in pharmacology},
year = {2026},
month = apr,
volume = {17},
pages = {1718110},
publisher = {Frontiers Media SA},
issn = {1663-9812},
doi = {10.3389/fphar.2026.1718110},
url = {https://doi.org/10.3389/fphar.2026.1718110},
pmid = {42064819},
pmcid = {PMC13125176}
}

RIS

TY - JOUR
AU - Chen, Yahong
AU - Zhu, Jie
AU - Li, Shuhuan
AU - Liang, Peishan
AU - Zhang, Yiqiong
AU - Ren, Guangli
TI - Protective role of miR-712-3p in heatstroke-induced brain injury: involvement of neuronal lysosomal function and association with astrocytic exosome-enriched preparations
T2 - Frontiers in pharmacology
J2 - Front Pharmacol
PY - 2026
DA - 2026/04/15
VL - 17
SP - 1718110
SN - 1663-9812
PB - Frontiers Media SA
DO - 10.3389/fphar.2026.1718110
UR - https://doi.org/10.3389/fphar.2026.1718110
LA - en
ER -

CSL-JSON

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"title": "Protective role of miR-712-3p in heatstroke-induced brain injury: involvement of neuronal lysosomal function and association with astrocytic exosome-enriched preparations",
"container-title": "Frontiers in pharmacology",
"author": [
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"family": "Chen",
"given": "Yahong"
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"volume": "17",
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"DOI": "10.3389/fphar.2026.1718110",
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"ISSN": "1663-9812",
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"language": "en",
"issued": {
"date-parts": [
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}

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