Exosome Derived From Human Umbilical Cord Mesenchymal Stem Cell Mediates MiR-181c Attenuating Burn-induced Excessive Inflammation

• hUCMSC-exosome administration attenuated burn-induced inflammation
• miR-181c in hUCMSC-exosome served an pivotal role in regulating inflammation
• miR-181c repressed burn-induced inflammation via targeting TLR4This study wants to address the potential function of exosomal miRNA on regulating burn-induced inflammation, and our results indicated that exosome derived from stem cells administration attenuated burn-induced inflammation of rats. Further study elucidated that miR-181c might serve an essential role in regulating inflammation. miR-181c suppressed toll-like receptor 4 expression, and subsequently reduced the expression of pro-inflammatory factors TNF-α, IL-1β. Forced expression of miR-181c in exosome further alleviated burn-induced inflammation. So our study provided a complete understanding of exosomal miR-181c in regulating burn-induced inflammation and its potentials as clinical therapeutic target of burn patients.

Mesenchymal stem cell (MSC)-derived exosomes have diverse functions in regulating wound healing and inflammation; however, the molecular mechanism of human umbilical cord MSC (hUCMSC)-derived exosomes in regulating burn-induced inflammation is not well understood. We found that burn injury significantly increased the inflammatory reaction of rats or macrophages exposed to lipopolysaccharide (LPS), increased tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) levels and decreased IL-10 levels. hUCMSC-exosome administration successfully reversed this reaction. Further studies showed that miR-181c in the exosomes played a pivotal role in regulating inflammation. Compared to control hUCMSC-exosomes, hUCMSC-exosomes overexpressing miR-181c more effectively suppressed the TLR4 signaling pathway and alleviated inflammation in burned rats. Administration of miR-181c-expressing hUCMSC-exosomes or TLR4 knockdown significantly reduced LPS-induced TLR4 expression by macrophages and the inflammatory reaction. In summary, miR-181c expression in hUCMSC-exosomes reduces burn-induced inflammation by downregulating the TLR4 signaling pathway.

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