MicroRNAs control intestinal epithelial differentiation, architecture, and barrier function.
MicroRNAs control intestinal epithelial differentiation, architecture, and barrier function.
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DOI：
10.1053/j.gastro.2010.07.040
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发表时间：
2010-11
期刊：
影响因子：
29.4
通讯作者：
Kaestner KH
中科院分区：
文献类型：
--
作者：
McKenna LB;Schug J;Vourekas A;McKenna JB;Bramswig NC;Friedman JR;Kaestner KH
虽然miRNA对于几种组织的发育和维持的重要性已经得到了很好的证实，但其在肠道中的作用尚不清楚。我们的目的是以定量的方式确定哺乳动物小肠的整个miRNA表达谱，并使用遗传手段确定miRNA对肠道发育和稳态的贡献。我们使用超高通量测序确定了小鼠肠上皮细胞的完整miRNA转录组。我们采用Dicer 1的基因切除来产生小鼠肠道中所有miRNA的缺陷小鼠。在哺乳动物小肠中，miRNA丰度在很大的动态范围内变化，从百万分之一到250，000。在所鉴定的453个miRNA家族中，mmu-miR-192和mmu-let-7是最高表达的。在形态学上，Dicer 1 loxP/loxP; Villin-Cre突变小鼠的小肠和大肠上皮细胞均紊乱，结肠杯状细胞减少4倍，大肠和小肠隐窝细胞凋亡急剧增加。此外，肠屏障功能依赖于miRNA的存在，因此Dicer 1缺陷小鼠表现出伴有淋巴细胞和中性粒细胞浸润的肠道炎症。我们已经鉴定了所有的肠道miRNAs，并使用Dicer 1的基因消融显示，miRNAs在肠上皮的分化和功能中起着至关重要的作用。
While the importance of miRNA for the development and maintenance of several tissues is well established, its role in the intestine is unknown. Our aims were to determine the entire miRNA expression profile of the mammalian small intestine in a quantitative manner and to determine the contribution of miRNAs to intestinal development and homeostasis using genetic means. We determined the complete miRNA transcriptome of the mouse intestinal epithelium using ultra-high throughput sequencing. We employed gene ablation of Dicer1 to generate mice deficient for all miRNAs in the mouse intestine. miRNA abundance varies over a large dynamic range in the mammalian small intestine, from one read per million to 250,000. Of the 453 miRNA families identified, mmu-miR-192 and mmu-let-7 are the most highly expressed. Morphologically, the epithelium of Dicer1loxP/loxP; Villin-Cre mutants mice is disorganized in both the small and large intestine, with a four-fold decrease in goblet cells in the colon and a dramatic increase in apoptosis in the crypts of both the large and small intestine. Furthermore, intestinal barrier function is dependent on the presence of miRNAs, and consequently Dicer1 deficient mice display intestinal inflammation with lymphocyte and neutrophil infiltration. We have identified all intestinal miRNAs and shown using gene ablation of Dicer1 that miRNAs play a vital role in the differentiation and function of the intestinal epithelium.
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影响因子：
10.5
作者：
Gupta, Rana K.;Gao, Nan;Kaestner, Klaus H.
通讯作者：
Kaestner, Klaus H.
DOI：
10.1016/j.bbrc.2009.11.052
发表时间：
2010-01-01
影响因子：
3.1
作者：
Simion, Alexandru;Laudadio, Ilaria;Jacquemin, Patrick
通讯作者：
Jacquemin, Patrick
DOI：
10.1073/pnas.091062498
发表时间：
2001-04-24
影响因子：
11.1
作者：
Tusher, VG;Tibshirani, R;Chu, G
通讯作者：
Chu, G
影响因子：
5.3
作者：
Liu, Y;Hedvat, CV;Nimer, SD
通讯作者：
Nimer, SD
影响因子：
2
作者：
Akao, Yukihiro;Nakagawa, Yoshihito;Naoe, Tomoki
通讯作者：
Naoe, Tomoki