miR-802 regulates Paneth cell function and enterocyte differentiation in the mouse small intestine.
miR-802 regulates Paneth cell function and enterocyte differentiation in the mouse small intestine.
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DOI：
10.1038/s41467-021-23298-3
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发表时间：
2021-06-07
影响因子：
16.6
通讯作者：
Stoffel M
中科院分区：
文献类型：
--
作者：
Goga A;Yagabasan B;Herrmanns K;Godbersen S;Silva PN;Denzler R;Zünd M;Furter M;Schwank G;Sunagawa S;Hardt WD;Stoffel M
肠上皮是一个复杂的结构，集消化、免疫、神经内分泌和再生功能于一体。上皮内稳态是通过不同上皮细胞类型的相互协调来维持的。肠上皮完整性的丧失在炎症性疾病和胃肠道感染中起着关键作用。在这里，我们发现富含肠道的miR-802是肠上皮细胞增殖、Paneth细胞功能和肠细胞分化的中心调节剂。小鼠小肠中mir-802的基因消融导致葡萄糖摄取减少，肠细胞分化受损，Paneth细胞功能增加和肠上皮细胞增殖。这些作用部分是通过miR-802靶点Tmed9的抑制介导的，Tmed9是Paneth细胞中Wnt和溶菌酶/防御素分泌的调节剂，以及下游Wnt信号成分Fzd5和Tcf4。携带miR-802结合位点突变的突变Tmed9小鼠部分再现了缺乏miR-802的小鼠的Paneth细胞功能增强。我们的研究表明，广泛的miR-802网络对于小肠中不同细胞类型控制上皮稳态的信号通路的整合是重要的。肠上皮的内稳态对维持上皮屏障至关重要。在这里，作者表明，小鼠肠道中mir-802的消融会损害肠细胞的分化和葡萄糖吸收，通过增加tmed9介导的防御素分泌来增强Paneth细胞的功能，并增加上皮细胞的更新。
The intestinal epithelium is a complex structure that integrates digestive, immunological, neuroendocrine, and regenerative functions. Epithelial homeostasis is maintained by a coordinated cross-talk of different epithelial cell types. Loss of integrity of the intestinal epithelium plays a key role in inflammatory diseases and gastrointestinal infection. Here we show that the intestine-enriched miR-802 is a central regulator of intestinal epithelial cell proliferation, Paneth cell function, and enterocyte differentiation. Genetic ablation of mir-802 in the small intestine of mice leads to decreased glucose uptake, impaired enterocyte differentiation, increased Paneth cell function and intestinal epithelial proliferation. These effects are mediated in part through derepression of the miR-802 target Tmed9, a modulator of Wnt and lysozyme/defensin secretion in Paneth cells, and the downstream Wnt signaling components Fzd5 and Tcf4. Mutant Tmed9 mice harboring mutations in miR-802 binding sites partially recapitulate the augmented Paneth cell function of mice lacking miR-802. Our study demonstrates a broad miR-802 network that is important for the integration of signaling pathways of different cell types controlling epithelial homeostasis in the small intestine. Homeostasis of the intestinal epithelium is crucial for the maintenance of the epithelial barrier. Here, the authors show that mir-802 ablation in the mouse intestine impairs enterocyte differentiation and glucose absorption, enhances Paneth cell function by increasing Tmed9-mediated defensin secretion, and increases epithelial cell turnover.
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影响因子：
7.3
作者：
Al-Barazie RM;Bashir GH;Qureshi MM;Mohamed YA;Al-Sbiei A;Tariq S;Lammers WJ;Al-Ramadi BK;Fernandez-Cabezudo MJ
通讯作者：
Fernandez-Cabezudo MJ
影响因子：
9.2
作者：
D'Arcangelo, Jennifer G.;Crissman, Jonathan;Pagant, Silvere;Copic, Alenka;Latham, Catherine F.;Snapp, Erik L.;Miller, Elizabeth A.
通讯作者：
Miller, Elizabeth A.
影响因子：
4.6
作者：
Andreu, P;Colnot, S;Romagnolo, B
通讯作者：
Romagnolo, B
影响因子：
1.4
作者：
Apprill, Amy;McNally, Sean;Weber, Laura
通讯作者：
Weber, Laura
影响因子：
5.3
作者：
Coant, Nicolas;Ben Mkaddem, Sanae;Ogier-Denis, Eric
通讯作者：
Ogier-Denis, Eric