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

Abstract

ObjectivesConfirm that stem cells from human exfoliated deciduous teeth‐derived exosomes (SHED‐exos) can limit inflammation‐triggered epithelial cell apoptosis and explore the molecular mechanism.MethodsSHED‐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.ResultsSHED‐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.ConclusionSHED‐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.

Lycopene from tomatoes and tomato products exerts renoprotective effects by ameliorating oxidative stress, apoptosis, pyroptosis, fibrosis, and inflammatory injury in calcium oxalate nephrolithiasis: the underlying mechanisms

“…Furthermore, activation of ERK1/2 signaling increases ROS production and apoptotic glandular cell numbers, and inhibition of ERK1/2 suppresses apoptotic cell numbers by decreasing cleaved caspase-3. 47,48 Our results indicated that the cell-damaging effects of increased ROS generation and apoptosis due to downregulated Trappc4 expression were eliminated when ERK1/2 signaling was inhibited. These findings emphasize the therapeutic potential of lycopene in the treatment of nephrolithiasis via the modulation of the Trappc4/ERK1/2 signaling pathway.…”