MSC-Derived Small Extracellular Vesicles Alleviate Diabetic Retinopathy by Delivering miR-22-3p to Inhibit NLRP3 Inflammasome Activation.
Stem Cells
; 42(1): 64-75, 2024 Jan 13.
Article
em En
| MEDLINE
| ID: mdl-37847598
ABSTRACT
PURPOSE:
This study aimed to investigate the effect of mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) on diabetic retinopathy (DR) and its underlying mechanism.METHODS:
In vivo, MSC-sEVs were injected intravitreally into diabetic rats to determine the therapeutic efficacy. In vitro, MSC-sEVs with/without miR-22-3p inhibition were cocultured with advanced glycation end-products (AGEs)-induced microglia with/without NLRP3 overexpression to explore the molecular mechanism.RESULTS:
In vivo, MSC-sEVs inhibited NLRP3 inflammasome activation, suppressed microglial activation, decreased inflammatory cytokines levels in the retina, and alleviated DR as evidenced by improved histological morphology and blood-retinal barrier function. Based on miRNA sequencing of MSC-sEVs, bioinformatic software, and dual-luciferase reporter assay, miR-22-3p stood out as the critical molecule for the role of MSC-sEVs in regulating NLRP3 inflammasome activation. Diabetic rats had lower level of miR-22-3p in their retina than those of control and sEV-treated rats. Confocal microscopy revealed that sEV could be internalized by microglia both in vivo and in vitro. In vitro, compared with sEV, the anti-inflammation effect of sEVmiR-22-3p(-) on AGEs-induced microglia was compromised, as they gave a lower suppression of NLRP3 inflammasome activation and inflammatory cytokines. In addition, NLRP3 overexpression in microglia damped the anti-inflammatory effect of sEV.CONCLUSION:
These results indicated that MSC-sEVs alleviated DR via delivering miR-22-3p to inhibit NLRP3 inflammasome activation. Our findings indicate that MSC-sEVs might be a potential therapeutic method for DR.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
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Diabetes Mellitus Experimental
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Retinopatia Diabética
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Células-Tronco Mesenquimais
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Vesículas Extracelulares
Limite:
Animals
Idioma:
En
Revista:
Stem Cells
Ano de publicação:
2024
Tipo de documento:
Article