Grape Exosome-like Nanoparticles Induce Intestinal Stem Cells and Protect Mice From DSS-Induced Colitis
Grape Exosome-like Nanoparticles Induce Intestinal Stem Cells and Protect Mice From DSS-Induced Colitis
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DOI：
10.1038/mt.2013.64
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发表时间：
2013-07-01
影响因子：
12.4
通讯作者：
Zhang, Huang-Ge
中科院分区：
文献类型：
--
作者：
Ju, Songwen;Mu, Jingyao;Zhang, Huang-Ge
食物来源的外泌体样纳米颗粒在我们的生活中通过肠道，但对其影响或功能知之甚少。在这里，作为概念的证明，我们表明葡萄外泌体样纳米颗粒（GELN）靶向的细胞是肠道干细胞，其反应是GELN介导的肠道组织重塑和保护免受葡聚糖硫酸钠（DSS）诱导的结肠炎的基础。这一发现进一步得到了以下事实的支持：将隐窝或分选的Lgr 5（+）干细胞与GELN共培养显著改善了类器官形成。GELN脂质在诱导Lgr 5（+）干细胞中发挥作用，而用GELN脂质组装的脂质体样纳米颗粒（LLN）是体内靶向肠道干细胞所需的。阻断GELN受体细胞的β-连环蛋白介导的信号传导途径会减弱Lgr 5（+）干细胞的产生。因此，GELN不仅调节肠组织更新过程，而且可以参与响应病理触发的肠组织重塑。
Food-derived exosome-like nanoparticles pass through the intestinal tract throughout our lives, but little is known about their impact or function. Here, as a proof of concept, we show that the cells targeted by grape exosome-like nanoparticles (GELNs) are intestinal stem cells whose responses underlie the GELN-mediated intestinal tissue remodeling and protection against dextran sulfate sodium (DSS)-induced colitis. This finding is further supported by the fact that coculturing of crypt or sorted Lgr5(+) stem cells with GELNs markedly improved organoid formation. GELN lipids play a role in induction of Lgr5(+) stem cells, and the liposome-like nanoparticles (LLNs) assembled with lipids from GELNs are required for in vivo targeting of intestinal stem cells. Blocking beta-catenin-mediated signaling pathways of GELN recipient cells attenuates the production of Lgr5(+) stem cells. Thus, GELNs not only modulate intestinal tissue renewal processes, but can participate in the remodeling of it in response to pathological triggers.