ArticleJournal of translational medicine2023
Dental pulp stem cell-derived exosomes revitalize salivary gland epithelial cell function in NOD mice via the GPER-mediated cAMP/PKA/CREB signaling pathway.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 3 of them syntheses that pooled it.
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Who cites it
37 citing papers in PubMed, 3 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- The Efficacy of Mesenchymal Stem Cell-Based Therapy for Sjögren's Syndrome: A Systematic Review and Meta-Analysis of Preclinical Studies.International dental journal · 2026Pooled it
- Harnessing exosomes in dry eye disease: a triple threat approach.BMC ophthalmology · 2026Pooled it
- Extracellular vesicles in dry eye disease and Sjögren's syndrome: A systematic review on their diagnostic and therapeutic role.Survey of ophthalmologyPooled it
- Efficacy of topical mesenchymal stem cell exosome in Sjögren's syndrome-related dry eye: a randomized clinical trial.BMC ophthalmology · 2025Trial
- Regenerative capacity of human dental pulp stem cells versus their exosomes on surgically induced submandibular gland defects in rats.BMC oral health · 2026Article
- Soluble Epoxide Hydrolase Inhibition Regulates Septoclast Activity to Promote Long Bone Growth and Fracture Healing by Enhancing Endothelial-to-Mesenchymal Notch Signalling.Cell proliferation · 2026Article
- M2 microglia-derived migrasome-enriched extracellular vesicles restore mitochondrial homeostasis to orchestrate neurovascular unit recovery after ischemic stroke.Journal of nanobiotechnology · 2026Article
- Enhancing exosomes efficacy with engineered nanozymes for a multi-targeted combination strategy in osteoarthritis treatment.Materials today. Bio · 2026Article
- CCR1Journal of advanced research · 2026Article
- UCMSC-derived exosomes ameliorate dry eye disease pathogenesis by modulating neutrophils on Th17/Treg balance.Scientific reports · 2026Article
- Tissue regeneration strategies based on mesenchymal stem cell-derived extracellular vesicles: from bench to bedside.Burns & trauma · 2026Review
- Diagnostic and therapeutic potential of oral cavity-derived exosomes in oral and maxillofacial tissue engineering: current advances and future perspectives.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Role of Mesenchymal Stem Cell Exosomes and Injectable Platelet Rich Fibrin on Structure and Function of Submandibular Salivary Gland of Aged Albino Rats.The Saudi dental journal · 2025Article
- Isolation methods of exosomes derived from dental stem cells.International journal of oral science · 2025Review
- Exosomes as immunomodulators in autoimmune inflammation: implications for primary Sjögren's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- M2-ApoBDs as a therapeutic strategy for systemic lupus erythematosus: targeted macrophage reprogramming and treg differentiation.Journal of nanobiotechnology · 2025Article
- Cellular Senescence Contributes to the Dysfunction of Tight Junctions in Submandibular Glands of Aging Mice.Aging cell · 2025Article
- Three-dimensional matrix stiffness-based stem cell soil: Tri-phase biomechanical structure promoted human dental pulp stem cells to achieve pulpodentin regeneration.Materials today. Bio · 2025Article
- Age-Related Oral and Para-Oral Tissue Disorders: The Evolving Therapeutic and Diagnostic Potential of Exosomes.Dentistry journal · 2025Review
- Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRestoration of salivary gland function in Sjogren's syndrome (SS) is still a challenge. Dental pulp stem cells (DPSCs) derived exosomes had shown anti-inflammatory, anti-oxidative, immunomodulatory, and tissue function restorative abilities. However, the salivary gland function restoration potential of DPSCs-derived exosomes (DPSC-Exos) during SS has not been investigated yet.
methodsDPSC-Exos was isolated by ultracentrifugation methods and characterized. Salivary gland epithelial cells (SGEC) were treated with interferon-gamma (IFN-γ) to mimic SS in vitro and cultured with or without DPSC-Exos. SGEC survival and aquaporin 5 (AQP5) expression were analyzed. mRNA sequencing and bioinformatics analysis were performed in IFN-γ vs. DPSC-Exos+ IFN-γ treated SGEC. Non-obese diabetic (NOD)/ltj female mice (SS model), were intravenously administered with DPSC-Exos, and salivary gland functions and SS pathogenicity were analyzed. Furthermore, the mRNA sequencing and bioinformatics predicted mechanism of the therapeutic effect of DPSC-Exos was further investigated both in vitro and in vivo using RT-qPCR, Western blot, immunohistochemistry, immunofluorescence, flowcytometry analysis.
resultsDPSC-Exos partially rescued IFN-γ triggered SGEC death. IFN-γ inhibited AQP5 expression in SGEC and DPSC-Exos reversed this effect. Transcriptome analysis showed GPER was the upregulated DEG in DPSC-Exos-treated SGEC with a positive correlation with salivary secretion-related DEGs. Pathway enrichment analysis revealed that DEGs were mainly attributed to estrogen 16 alpha-hydroxylase activity, extracellular exosome function, cAMP signaling, salivary secretion, and estrogen signaling. Intravenous injection of DPSC-Exos in NOD/ltj mice alleviated the SS syndrome as indicated by the increased salivary flow rate, attenuated glandular inflammation, and increased AQP5 expression. GPER was also upregulated in the salivary gland of DPSC-Exos-treated NOD/ltj mice compared with the PBS-treated NOD/ltj mice. IFN-γ+DPSC-Exos-treated SGEC showed higher expression of AQP5, p-PKA, cAMP, and intracellular Ca
conclusionsOur results showed that DPSC-Exos revitalize salivary gland epithelial cell function during SS via the GPER-mediated cAMP/PKA/CREB pathway suggesting the possible therapeutic potential of DPSC-Exos in SS-treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.