Exosome Derived From Human Umbilical Cord Mesenchymal Stem Cell Mediates MiR-181c Attenuating Burn-induced Excessive Inflammation.
Exosome Derived From Human Umbilical Cord Mesenchymal Stem Cell Mediates MiR-181c Attenuating Burn-induced Excessive Inflammation.
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源自人脐带间充质干细胞的外泌体介导 MiR-181c 减轻烧伤引起的过度炎症。
DOI：
10.1016/j.ebiom.2016.04.030
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发表时间：
2016-06
期刊：
影响因子：
11.1
通讯作者：
Yin H
中科院分区：
文献类型：
--
作者：
Li X;Liu L;Yang J;Yu Y;Chai J;Wang L;Ma L;Yin H
间充质干细胞(MSC)来源的外切体在调节创面愈合和炎症方面具有多种功能，然而，人脐带间充质干细胞(HUCMSC)来源的外切体在调节烧伤炎症中的分子机制尚不清楚。结果发现，烧伤后大鼠或巨噬细胞对内毒素的炎症反应明显增加，肿瘤坏死因子α和白细胞介素1α(IL-1β)水平升高，IL-10水平降低。HUCMSC-exosome给药成功逆转这一反应。进一步的研究表明，外切体中的miR-181c在调节炎症中起着关键作用。与对照hUCMSC-exosome相比，高表达miR-181c的hUCMSC-exosome更有效地抑制了TLR4信号通路，减轻了烧伤大鼠的炎症反应。表达miR-181c的hUCMSC-exosome或TLR4基因敲除后，巨噬细胞表达TLR4和炎症反应明显减少。综上所述，miR-181c在hUCMSC-exosome中的表达通过下调TLR4信号通路来减轻烧伤引起的炎症反应。HUCMSC-exosome通过靶向TLR4抑制烧伤炎症miR-181c在炎症调控中发挥关键作用本研究旨在探讨外体miRNA在调节烧伤炎症中的作用，我们的研究结果表明，干细胞注射产生的exosome可减轻大鼠烧伤后的炎症反应。进一步的研究表明miR-181c可能在调节炎症中发挥重要作用。MIR-181c抑制Toll样受体4的表达，进而降低促炎因子肿瘤坏死因子-α、IL-1β的表达。外体强制表达miR-181c可进一步减轻烧伤后炎症反应。本研究为进一步了解外体miR-181c在调节烧伤炎症反应中的作用及其作为烧伤患者临床治疗靶点的潜力提供了理论依据。
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. 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 TLR4 This 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.