ArticleJournal of advanced research2026
Exosomes derived from M1-macrophage promote enteric neuronal injury via MMP8-TGF-β pathway.
Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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Who cites it
3 citing papers in PubMed.
- Macrophage-enteric nervous system crosstalk in Hirschsprung disease and associated enterocolitis: a focused narrative review with clinical implications.Pediatric surgery international · 2026Review
- Pathological mechanisms and therapeutic potential of MSC-Exos in ischemic stroke management.Stem cell research & therapy · 2026Review
- Review
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionEnteric neuronal injury significantly contributes to gastrointestinal motility disorders. While macrophages are known to interact closely with enteric neurons and modulate intestinal homeostasis, their specific impact on enteric neuronal survival and injury remains poorly understood.
objectiveThis study aimed to explore the potential contribution of macrophage-derived exosomes to enteric neuronal injury and investigate the underlying mechanisms.
methodsWe established a benzalkonium chloride (BAC)-induced enteric neuronal injury mouse model and assessed the effects of macrophage depletion on gastrointestinal motility and neuronal density. In vitro, enteric neurons were co-cultured with macrophages to examine the role of macrophage-derived exosomes in neuronal apoptosis. M1 macrophage-derived exosomes were isolated and characterized to elucidate potential mechanisms both in vitro and in vivo.
resultsMacrophage depletion partially rescued gastrointestinal dysmotility and enteric neuronal injury in BAC-treated mice. In vitro studies confirmed that M1 macrophage-derived exosomes promoted neuronal apoptosis. We identified matrix metalloproteinase 8 (MMP8) as enriched in M1 macrophage-derived exosomes, promoting the activation of the TGF-β signaling pathway and inducing neuronal apoptosis. Exosomes derived from M1 macrophages exacerbated neuronal injury in BAC mice, while inhibiting MMP8 partially mitigated neuronal injury and restored intestinal function. Additionally, elevated serum exosomal MMP8 levels were identified as a potential marker for Hirschsprung's disease, a typical gastrointestinal motility disorder.
conclusionM1 macrophages induce enteric neuronal injury via exosomal MMP8-mediated TGF-β signaling, highlighting a potential therapeutic target for gastrointestinal motility disorders.
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