Extracellular Vesicles Derived from Bone Marrow Mesenchymal Stem Cells Protect against Experimental Colitis via Attenuating Colon Inflammation, Oxidative Stress and Apoptosis.
Extracellular Vesicles Derived from Bone Marrow Mesenchymal Stem Cells Protect against Experimental Colitis via Attenuating Colon Inflammation, Oxidative Stress and Apoptosis.
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骨髓间充质干细胞衍生的细胞外囊泡通过减轻结肠炎症、氧化应激和细胞凋亡来预防实验性结肠炎
DOI：
10.1371/journal.pone.0140551
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Liu YJ
中科院分区：
文献类型：
--
作者：
Yang J;Liu XX;Fan H;Tang Q;Shou ZX;Zuo DM;Zou Z;Xu M;Chen QY;Peng Y;Deng SJ;Liu YJ
骨髓间充质干细胞(BMSCs)可逆转实验性结肠炎，其组织修复机制可能与其旁分泌活性有关。骨髓间充质干细胞来源的胞外囊泡(BMSC-EV)包括微囊泡和外体，含有多种蛋白质、mRNAs和microRNAs，介导多种生物学功能，可能是干细胞与损伤细胞通讯的主要旁分泌机制。本研究旨在探讨BMSC-EVS对2，4，6-三硝基苯磺酸(TNBS)诱导的大鼠结肠炎模型的治疗作用。静脉注射BMSC-EVS可减轻结肠炎的严重程度，表现为疾病活动指数(DAI)和结肠组织学损害。在炎症反应中，BMSC-EVS治疗组大鼠损伤结肠组织中核因子-κ-Bp65、肿瘤坏死因子-α、诱导型一氧化氮合酶和环氧合酶-2的基因和蛋白表达均显著降低。此外，骨髓间充质干细胞-EVS注射后，IL-1β(IL-1β)显著降低，IL-10(IL-10)表达增加。BMSC-EVS的治疗作用与抑制氧化紊乱有关，表现为降低髓过氧化物酶(MPO)和丙二醛(MDA)活性，升高超氧化物歧化酶(SOD)和谷胱甘肽(GSH)。BMSC-EVS还通过减少caspase-3、caspase-8和caspase-9的裂解而抑制结肠炎大鼠的细胞凋亡。研究表明，BMSC-EVS的有益作用是通过下调促炎细胞因子水平，抑制NF-κBp65信号转导通路，调节抗氧化/氧化平衡，减缓细胞凋亡的发生。
The administration of bone mesenchymal stem cells (BMSCs) could reverse experimental colitis, and the predominant mechanism in tissue repair seems to be related to their paracrine activity. BMSCs derived extracellular vesicles (BMSC-EVs), including mcirovesicles and exosomes, containing diverse proteins, mRNAs and micro-RNAs, mediating various biological functions, might be a main paracrine mechanism for stem cell to injured cell communication. We aimed to investigate the potential alleviating effects of BMSC-EVs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Intravenous injection of BMSC-EVs attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI) and histological colonic damage. In inflammation response, the BMSC-EVs treatment significantly reduced both the mRNA and protein levels of nuclear factor kappaBp65 (NF-κBp65), tumor necrosis factor-alpha (TNF-α), induciblenitric oxidesynthase (iNOS) and cyclooxygenase-2 (COX-2) in injured colon. Additionally, the BMSC-EVs injection resulted in a markedly decrease in interleukin-1β (IL-1β) and an increase in interleukin-10 (IL-10) expression. Therapeutic effect of BMSC-EVs associated with suppression of oxidative perturbations was manifested by a decrease in the activity of myeloperoxidase (MPO) and Malondialdehyde (MDA), as well as an increase in superoxide dismutase (SOD) and glutathione (GSH). BMSC-EVs also suppressed the apoptosis via reducing the cleavage of caspase-3, caspase-8 and caspase-9 in colitis rats. Data obtained indicated that the beneficial effects of BMSC-EVs were due to the down regulation of pro-inflammatory cytokines levels, inhibition of NF-κBp65 signal transduction pathways, modulation of anti-oxidant/ oxidant balance, and moderation of the occurrence of apoptosis.