TSG-6 Secreted by Human Adipose Tissue-derived Mesenchymal Stem Cells Ameliorates DSS-induced colitis by Inducing M2 Macrophage Polarization in Mice.
TSG-6 Secreted by Human Adipose Tissue-derived Mesenchymal Stem Cells Ameliorates DSS-induced colitis by Inducing M2 Macrophage Polarization in Mice.
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DOI：
10.1038/s41598-017-04766-7
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发表时间：
2017-07-12
影响因子：
4.6
通讯作者：
Youn HY
中科院分区：
文献类型：
--
作者：
Song WJ;Li Q;Ryu MO;Ahn JO;Ha Bhang D;Chan Jung Y;Youn HY
先前的研究表明，间充质干细胞（MSC）通过调节炎症肠道中的炎症细胞因子来缓解炎症性肠病（IBD）。然而，这些影响的机制尚未完全了解。我们试图研究人脂肪组织来源的（hAT）-MSC在IBD小鼠模型中的治疗效果，并探索炎症调节的机制。将葡聚糖硫酸钠诱导的结肠炎小鼠腹膜内输注hAT-MSC，并在第10天收集结肠组织。hAT-MSC显示诱导M2巨噬细胞标志物的表达并调节结肠中促炎和抗炎细胞因子的表达。定量真实的时间PCR分析表明，在发炎的结肠中检测到少于20个hAT-MSC，占所有腹腔注射的hAT-MSC的0.001%。为了研究hAT-MSC分泌因子的体外作用，采用transwell共培养系统，证明hAT-MSC分泌的肿瘤坏死因子-α诱导的基因/蛋白6（TSG-6）诱导M2巨噬细胞。在体内，用TSG-6小干扰RNA转染的hAT-MSC，腹腔内给药，不能诱导炎症结肠中的M2巨噬细胞表型转换，并且对IBD的严重程度没有显著影响。结论：hAT-MSC产生的TSG-6可通过诱导小鼠M2巨噬细胞转换来改善IBD。
Previous studies have revealed that mesenchymal stem cells (MSCs) alleviate inflammatory bowel disease (IBD) by modulating inflammatory cytokines in the inflamed intestine. However, the mechanisms underlying these effects are not completely understood. We sought to investigate the therapeutic effects of human adipose tissue-derived (hAT)-MSCs in an IBD mouse model and to explore the mechanisms of the regulation of inflammation. Dextran sulfate sodium-induced colitis mice were infused with hAT-MSCs intraperitoneally and colon tissues were collected on day 10. hAT-MSCs were shown to induce the expression of M2 macrophage markers and to regulate the expression of pro- and anti-inflammatory cytokines in the colon. Quantitative real time-PCR analyses demonstrated that less than 20 hAT-MSCs, 0.001% of all intraperitoneally injected hAT-MSCs, were detected in the inflamed colon. To investigate the effects of hAT-MSC-secreted factors in vitro, transwell co-culture system was used, demonstrating that tumour necrosis factor-α-induced gene/protein 6 (TSG-6) released by hAT-MSCs induces M2 macrophages. In vivo, hAT-MSCs transfected with TSG-6 small interfering RNA, administered intraperitoneally, were not able to induce M2 macrophage phenotype switch in the inflamed colon and had no significant effects on IBD severity. In conclusion, hAT-MSC-produced TSG-6 can ameliorate IBD by inducing M2 macrophage switch in mice.
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作者：
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通讯作者：
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