title: Exosome Derived From Human Umbilical Cord Mesenchymal Stem Cell Mediates MiR-181c Attenuating Burn-induced Excessive Inflammation.
abstract: 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.
authors.affiliation: Department of Burn & Plastic Surgery, The First Affiliated Hospital to PLA General Hospital, Beijing 100048, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Burn & Plastic Surgery, The First Affiliated Hospital to PLA General Hospital, Beijing 100048, China.
authors.forename: Lingying
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Burn & Plastic Surgery, The First Affiliated Hospital to PLA General Hospital, Beijing 100048, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Burn & Plastic Surgery, The First Affiliated Hospital to PLA General Hospital, Beijing 100048, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Burn & Plastic Surgery, The First Affiliated Hospital to PLA General Hospital, Beijing 100048, China. Electronic address: cjk304@126.com.
authors.forename: Jiake
authors.initials: J
authors.lastname: Chai
authors.affiliation: Department of Medical Administration, The First Affiliated Hospital to PLA General Hospital, Beijing 100048, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Burn & Plastic Surgery, The First Affiliated Hospital to PLA General Hospital, Beijing 100048, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Burn & Plastic Surgery, The First Affiliated Hospital to PLA General Hospital, Beijing 100048, China.
authors.forename: Huinan
authors.initials: H
authors.lastname: Yin
mesh_terms: D000818:Animals; D015415:Biomarkers; D002056:Burns / Q000150:complications*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D055354:Exosomes / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D010641:Phenotype; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C000608460:MIRN-181 microRNA, human; D035683:MicroRNAs; D051197:Toll-Like Receptor 4
keywords: Burn; Exosome; Inflammation; miR-181c