PepT1 Expression Helps Maintain Intestinal Homeostasis by Mediating the Differential Expression of miRNAs along the Crypt-Villus Axis.
PepT1 Expression Helps Maintain Intestinal Homeostasis by Mediating the Differential Expression of miRNAs along the Crypt-Villus Axis.
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DOI：
10.1038/srep27119
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发表时间：
2016-06-01
影响因子：
4.6
通讯作者：
Merlin D
中科院分区：
文献类型：
--
作者：
Zhang Y;Viennois E;Zhang M;Xiao B;Han MK;Walter L;Garg P;Merlin D
在空肠中，PepT 1特别富集在绒毛中分化良好的吸收上皮细胞中。对PepT 1沿着隐窝-绒毛轴的表达和功能的研究表明，该蛋白对二/三肽吸收过程至关重要。我们最近发现PepT 1在多种生物学功能中起着重要作用，包括调节特定microRNA（miRNAs）的表达/分泌和多种蛋白质的表达水平的能力。在这项研究中，我们观察到PepT 1基因敲除（KO）小鼠表现出体重减轻和肠道微绒毛缩短。然后，我们检查了PepT 1 KO小鼠空肠中沿着隐窝-绒毛轴的各种miRNA及其靶蛋白沿着的表达水平。我们发现PepT 1 KO改变了microRNA沿着绒毛轴的分布，并改变了绒毛和隐窝的microRNA谱。使用绒毛和隐窝样本的miRNA靶点预测和2D-DIGE/质谱，我们发现PepT 1的消融进一步直接或间接改变了某些蛋白质靶点的表达水平。总的来说，我们的研究结果表明，PepT 1有助于维持小肠内稳态和正常功能的平衡，并且沿着隐窝-绒毛轴沿着失调的miRNA和蛋白质与这一过程高度相关。
In the jejunum, PepT1 is particularly enriched in the well-differentiated absorptive epithelial cells in the villi. Studies of expression and function of PepT1 along the crypt-villus axis demonstrated that this protein is crucial to the process of di/tripeptide absorption. We recently exhibited that PepT1 plays an important role in multiple biological functions, including the ability to regulate the expression/secretion of specific microRNAs (miRNAs) and the expression levels of multiple proteins. In this study, we observed that PepT1 knockout (KO) mice exhibited reduced body weight and shorten intestinal microvilli. We then examined the expression levels of various miRNAs and their target proteins along the crypt-villi axis in the jejunum of PepT1 KO mice. We found that PepT1 KO altered the distribution of miRNAs along the crypt-villus axis and changed the miRNA profiles of both villi and crypts. Using miRNA-target prediction and 2D-DIGE/mass spectrometry on villi and crypts samples, we found that ablation of PepT1 further directly or indirectly altered expression levels of certain protein targets. Collectively, our results suggest that PepT1 contributes to maintain balance of homeostasis and proper functions in the small intestine, and dysregulated miRNAs and proteins along the crypt-villus axis are highly related to this process.