Distinct Age-Specific miRegulome Profiling of Isolated Small and Large Intestinal Epithelial Cells in Mice.
Distinct Age-Specific miRegulome Profiling of Isolated Small and Large Intestinal Epithelial Cells in Mice.
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DOI：
10.3390/ijms22073544
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发表时间：
2021-03-29
影响因子：
5.6
通讯作者：
Park EJ
中科院分区：
文献类型：
--
作者：
Lee J;Mohsen A;Banerjee A;McCullough LD;Mizuguchi K;Shimaoka M;Kiyono H;Park EJ
肠上皮作为一种动态屏障，保护宿主组织免受肠道环境中无数炎症刺激的影响。肠上皮细胞（IECs）包括分化和特化的细胞类型，它们配备了调节基因，可以感知腔内环境。潜在的炎症线索可以指示iec经历多种表型改变。衰老是多种疾病的主要危险因素；现在有充分的证据表明，衰老本身会降低肠上皮的屏障功能和更新，导致病原体易位和免疫启动，并增加全身炎症。在这项研究中，我们的目的是提供一个有效的表观遗传学和调控前景，通过分析分离小鼠iec上的microRNAs （miRNAs）来检查肠道中与年龄相关的变化。我们的微阵列分析显示，随着年龄的增长，与大IECs（3个mirna）相比，小IECs（22个mirna）中存在更大程度的不同mirna簇失调。此外，miRNA-mRNA相互作用网络和通路分析表明，衰老对小IECs（如toll样受体相关级联）和大IECs（如细胞周期、Notch信号和小泛素相关修饰因子途径）之间的关键通路有差异调节。综上所述，目前的研究结果提示了胃肠道组织衰老过程中上皮mirna的新基因调控途径。
The intestinal epithelium serves as a dynamic barrier to protect the host tissue from exposure to a myriad of inflammatory stimuli in the luminal environment. Intestinal epithelial cells (IECs) encompass differentiated and specialized cell types that are equipped with regulatory genes, which allow for sensing of the luminal environment. Potential inflammatory cues can instruct IECs to undergo a diverse set of phenotypic alterations. Aging is a primary risk factor for a variety of diseases; it is now well-documented that aging itself reduces the barrier function and turnover of the intestinal epithelium, resulting in pathogen translocation and immune priming with increased systemic inflammation. In this study, we aimed to provide an effective epigenetic and regulatory outlook that examines age-associated alterations in the intestines through the profiling of microRNAs (miRNAs) on isolated mouse IECs. Our microarray analysis revealed that with aging, there is dysregulation of distinct clusters of miRNAs that was present to a greater degree in small IECs (22 miRNAs) compared to large IECs (three miRNAs). Further, miRNA–mRNA interaction network and pathway analyses indicated that aging differentially regulates key pathways between small IECs (e.g., toll-like receptor-related cascades) and large IECs (e.g., cell cycle, Notch signaling and small ubiquitin-related modifier pathway). Taken together, current findings suggest novel gene regulation pathways by epithelial miRNAs in aging within the gastrointestinal tissues.
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影响因子：
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通讯作者：
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