SHED-exos promote saliva secretion by suppressing p-ERK1/2-mediated apoptosis in glandular cells.
Oral Dis
; 2023 Oct 17.
Article
em En
| MEDLINE
| ID: mdl-37849447
ABSTRACT
OBJECTIVES:
Confirm that stem cells from human exfoliated deciduous teeth-derived exosomes (SHED-exos) can limit inflammation-triggered epithelial cell apoptosis and explore the molecular mechanism.METHODS:
SHED-exos were injected into the submandibular glands (SMGs) of non-obese diabetic (NOD) mice, an animal model of Sjögren's syndrome (SS). Cell death was evaluated by western blotting and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining.RESULTS:
SHED-exos treatment promoted the saliva flow rates of NOD mice, accompanied by decreased cleaved caspase-3 levels and apoptotic cell numbers in SMGs. SHED-exos inhibited autophagy, pyroptosis, NETosis, ferroptosis, necroptosis and oxeiptosis marker expression in SS-damaged glands. Mechanistically, Kyoto Encyclopedia of Genes and Genomes analysis of exosomal miRNAs suggested that the rat sarcoma virus (RAS)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway might play an important role. In vivo, the expression of Kirsten RAS, Harvey RAS, MEK1/2 and p-ERK1/2 was upregulated in SMGs, and this change was blocked by SHED-exos treatment. In vitro, SHED-exos suppressed p-ERK1/2 activation and increased cleaved caspase-3 and apoptotic cell numbers, which were induced by IFN-γ.CONCLUSION:
SHED-exos suppress epithelial cell death, which is responsible for promoting salivary secretion. SHED-exos inhibited inflammation-triggered epithelial cell apoptosis by suppressing p-ERK1/2 activation, which is involved in these effects.
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Base de dados:
MEDLINE
Idioma:
En
Revista:
Oral Dis
Assunto da revista:
ODONTOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article