Adipose-derived mesenchymal stem cell-derived exosomal miR-22-3p alleviates depression-like behaviors in a rat model via the FURIN/HMGB1 axis
5 affiliations
- 1Guangxi University of Chinese Medicine
- 2The Second Affiliated Hospital of Guangxi University of Chinese
- 3Guangxi University
- 4Department of Psychiatry and Psychology, People’s Hospital of Guangxi Zhuang Autonomous Region
- 5Department of Anesthesiology, The Second Affiliated Hospital of Guangdong Medical University
Abstract
Background: Major depressive disorder (MDD) is characterized by neuroinflammation and neuronal apoptosis, yet effective brain-targeted delivery strategies remain limited. Exosomes represent promising carriers capable of crossing the blood–brain barrier. This study investigated whether engineered exosomes delivering miR-22-3p by modulating the FURIN/HMGB1 axis.
Methods: Serum microRNA expression was assessed in patients with MDD. A rat model of depression was established using chronic unpredictable mild stress (CUMS). miR-22-3p-engineered adipose-derived mesenchymal stem cell exosomes were administered intranasally. Behavioral tests (SPT, OFT, FST), RT-qPCR, ELISA, HE staining, and TUNEL assays were performed to evaluate neurobehavioral and molecular changes.
Results: miR-22-3p was significantly downregulated in both MDD patients and CUMS rats (P < 0.01). Intranasal administration of engineered exosomes increased brain miR-22-3p levels and significantly improved depressive-like behaviors (P < 0.05 or P < 0.01). Mechanistically, treatment suppressed FURIN and HMGB1 expression, reduced proinflammatory cytokines (IL-1β, IL-6, TNF-α), and attenuated hippocampal neuronal apoptosis (P < 0.05 or P < 0.01). These effects were more pronounced than those of native exosomes.
Conclusions: miR-22-3p-engineered exosomes exert antidepressant effects by inhibiting the FURIN/HMGB1-mediated neuroinflammatory and apoptotic pathways. This study highlights a novel intranasal exosome-based microRNA delivery strategy for MDD.
Related
- Plasma exosomal miR-25-3p alleviates acute pancreatitis-associated lung injury by inhibiting ferroptosis of type II alveolar epithelial cells via NOX4/NCOA4-mediated ferritinophagy
- Adipose-derived stem cell-derived extracellular vesicles promote critical-sized bone defect repair by enhancing the homing of bone marrow mesenchymal stem cells
- Bone Marrow Mesenchymal Stem Cell-Derived Exosomal miR-451a Inhibits Macrophage M1 Polarization Through the TLR4/PI3K/AKT Signaling Pathway to Alleviate Acute Lung Injury.
- Epithelial-endothelial barrier dysfunction and oxidative stress in ARDS subphenotypes: comparative efficacy of extracellular vesicles derived from bone marrow (MSC-EVs) and adipose tissue (ASC-EVs) mesenchymal stem cells
- Ginsenoside Rd alleviates atherosclerosis by inhibiting adipocyte ferroptosis in perivascular adipose tissues
BibTeX
@article{xu2026adiposederived,
title = {{Adipose-derived mesenchymal stem cell-derived exosomal miR-22-3p alleviates depression-like behaviors in a rat model via the FURIN/HMGB1 axis}},
author = {Yuxin Xu and Yanqiu You and Dekai Wei and Rong Liang and Weiping Liang and Bingzheng Feng and Jibing Chen and Jia Liang and Fujun Li},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1924891},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1924891/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Adipose-derived mesenchymal stem cell-derived exosomal miR-22-3p alleviates depression-like behaviors in a rat model via the FURIN/HMGB1 axis
AU - Yuxin Xu
AU - Yanqiu You
AU - Dekai Wei
AU - Rong Liang
AU - Weiping Liang
AU - Bingzheng Feng
AU - Jibing Chen
AU - Jia Liang
AU - Fujun Li
PY - 2026
DA - 2026/10/13
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1924891
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1924891/full
AB - Background: Major depressive disorder (MDD) is characterized by neuroinflammation and neuronal apoptosis, yet effective brain-targeted delivery strategies remain limited. Exosomes represent promising carriers capable of crossing the blood–brain barrier. This study investigated whether engineered exosomes delivering miR-22-3p by modulating the FURIN/HMGB1 axis. Methods: Serum microRNA expression was assessed in patients with MDD. A rat model of depression was established using chronic unpredictable mild stress (CUMS). miR-22-3p-engineered adipose-derived mesenchymal stem cell exosomes were administered intranasally. Behavioral tests (SPT, OFT, FST), RT-qPCR, ELISA, HE staining, and TUNEL assays were performed to evaluate neurobehavioral and molecular changes. Results: miR-22-3p was significantly downregulated in both MDD patients and CUMS rats (P < 0.01). Intranasal administration of engineered exosomes increased brain miR-22-3p levels and significantly improved depressive-like behaviors (P < 0.05 or P < 0.01). Mechanistically, treatment suppressed FURIN and HMGB1 expression, reduced proinflammatory cytokines (IL-1β, IL-6, TNF-α), and attenuated hippocampal neuronal apoptosis (P < 0.05 or P < 0.01). These effects were more pronounced than those of native exosomes. Conclusions: miR-22-3p-engineered exosomes exert antidepressant effects by inhibiting the FURIN/HMGB1-mediated neuroinflammatory and apoptotic pathways. This study highlights a novel intranasal exosome-based microRNA delivery strategy for MDD.
SN - 1663-9812
ER -