Enteric Nervous System Regulation of Intestinal Stem Cell Differentiation and Epithelial Monolayer Function.
Enteric Nervous System Regulation of Intestinal Stem Cell Differentiation and Epithelial Monolayer Function.
复制标题
DOI：
10.1038/s41598-018-24768-3
复制
发表时间：
2018-04-20
影响因子：
4.6
通讯作者：
Koppes A
中科院分区：
文献类型：
--
作者：
Puzan M;Hosic S;Ghio C;Koppes A
肠神经系统（ENS）是一个由神经元和神经胶质组成的复杂网络，它调节整个胃肠道（GI）的感觉运动功能。在这里，我们研究了ENS和肠肌成纤维细胞通过调节单层通透性、细胞因子的产生和肠干细胞的分化来维持原代肠上皮屏障的作用。利用一种新颖的体外transwell共培养系统，分离小鼠小肠干细胞并与ENS神经元和胶质细胞或上皮下肌成纤维细胞一起培养。结果表明，ENS有助于调节肠道干细胞的命运，促进向化学感觉肠内分泌细胞的分化，与ENS共同培养时，有0.9%的细胞表达嗜铬粒蛋白A，与肌成纤维细胞共培养时为0.6%，上皮细胞单独培养时为0.3%。此外，肠神经元和肌成纤维细胞在与肠上皮细胞共培养时释放细胞因子巨噬细胞炎症蛋白2 （MIP-2）、转化生长因子β1 （TGF-β1）和白细胞介素10 （IL-10）的差异，与与肌成纤维细胞共培养相比，ENS共培养中IL-10和MIP-2分别增加1.5倍和3倍。这些结果表明肠道种群在肠屏障功能调节中的重要性。
The Enteric Nervous System (ENS) is a complex network of neurons and glia, which regulates sensorimotor function throughout the gastroinestinal tract (GI). Here we investigated the role of the ENS and intestinal myofibroblasts in the maintenance of a primary intestinal epithelial barrier through regulation of monolayer permeability, cytokine production, and differentiation of intestinal stem cells. Utilizing a novel, in vitro, transwell-based coculture system, murine small intestinal stem cells were isolated and cultured with ENS neurons and glia or subepithelial myofibroblasts. Results show that the ENS contributes to regulation of intestinal stem cell fate, promoting differentiation into chemosensory enteroendocrine cells, with 0.9% of cells expressing chromogranin A when cultured with ENS versus 0.6% in cocultures with myofibroblasts and 0.3% in epithelial cultures alone. Additionally, enteric neurons and myofibroblasts differentially release cytokines Macrophage Inflammatory Protein 2 (MIP-2), Transforming Growth Factor beta 1 (TGF-β1), and Interleukin 10 (IL-10) when cultured with intestinal epithelial cells, with a 1.5 fold increase of IL-10 and a 3 fold increase in MIP-2 in ENS cocultures compared to coculture with myofibroblasts. These results indicate the importance of enteric populations in the regulation of intestinal barrier function.
登录
查看更多内容
DOI：
10.1152/ajpgi.00066.2003
发表时间：
2003-11-01
影响因子：
4.5
作者：
Neunlist, M;Toumi, F;Jarry, A
通讯作者：
Jarry, A
影响因子：
24.5
作者：
Aubé, AC;Cabarrocas, J;Neunlist, M
通讯作者：
Neunlist, M
影响因子：
3.7
作者：
Al-Sadi R;Ye D;Boivin M;Guo S;Hashimi M;Ereifej L;Ma TY
通讯作者：
Ma TY
影响因子：
3.7
作者：
Kuhn KA;Manieri NA;Liu TC;Stappenbeck TS
通讯作者：
Stappenbeck TS
影响因子：
15.9
作者：
Bohorquez, Diego V.;Shahid, Rafiq A.;Liddle, Rodger A.
通讯作者：
Liddle, Rodger A.