SHED-exos promote saliva secretion by suppressing p-ERK1/2-mediated apoptosis in glandular cells.

Autor: Chu WX; Department of Periodontics, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, P.R. China.; Center Laboratory, Peking University School and Hospital of Stomatology, Beijing, P.R. China., Ding C; Center Laboratory, Peking University School and Hospital of Stomatology, Beijing, P.R. China., Du ZH; Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, P.R. China., Wei P; Department of Oral Medicine, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, P.R. China., Wang YX; Center Laboratory, Peking University School and Hospital of Stomatology, Beijing, P.R. China., Ge XJ; Department of Periodontics, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, P.R. China., Yu GY; Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
Jazyk: angličtina
Zdroj: Oral diseases [Oral Dis] 2024 Jul; Vol. 30 (5), pp. 3066-3080. Date of Electronic Publication: 2023 Oct 17.
DOI: 10.1111/odi.14776
Abstrakt: 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.
(© 2023 The Authors. Oral Diseases published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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