证实来自人脱落乳牙源性外泌体（SHED-exos）的干细胞可以限制炎症引发的上皮细胞凋亡并探索分子机制。SHED-exos被注射到非肥胖糖尿病（NOD）的颌下腺（SMG）中）小鼠，干燥综合征（SS）的动物模型。通过蛋白质印迹和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记染色来评估细胞死亡。SHED-exos 处理促进了 NOD 小鼠的唾液流速，同时降低了 SMG 中裂解的 caspase-3 水平和凋亡细胞数量。 SHED-exos 抑制 SS 损伤腺体中的自噬、细胞焦亡、NETosis、铁死亡、坏死性凋亡和氧化死亡标志物表达。从机制上讲，京都基因和基因组百科全书对外泌体 miRNA 的分析表明，大鼠肉瘤病毒 (RAS)/丝裂原激活蛋白激酶激酶 (MEK)/细胞外信号调节激酶 (ERK) 通路可能发挥重要作用。在体内，SMG 中 Kirsten RAS、Harvey RAS、MEK1/2 和 p-ERK1/2 的表达上调，而这种变化可被 SHED-exos 治疗所阻断。在体外，SHED-exos 抑制 p-ERK1/2 激活并增加由 IFN-γ 诱导的裂解 caspase-3 和凋亡细胞数量。SHED-exos 抑制上皮细胞死亡，而上皮细胞死亡负责促进唾液分泌。 SHED-exos 通过抑制 p-ERK1/2 激活来抑制炎症引发的上皮细胞凋亡，p-ERK1/2 激活参与了这些效应。© 2023 作者。 《口腔疾病》由 Wiley periodicals LLC 出版。

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.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.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.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.