Epithelial response to a high-protein diet in rat colon

Epithelial response to a high-protein diet in rat colon
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DOI:
10.1186/s12864-017-3514-z
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发表时间:
2017-01-31
期刊:
影响因子:
4.4
通讯作者:
Lan, Annaig
Lan, Annaig
中科院分区:
生物学2区
文献类型:
--
作者:
Beaumont, Martin;Andriamihaja, Mireille;Lan, Annaig

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背景资料:高蛋白饮食(HPD)改变了大肠菌群的组成,与蛋白质降解的代谢转变有关。由结肠细菌产生的一些氨基酸衍生的代谢物对粘膜有益,而其他代谢物在高浓度下是有害的。本工作的目的是确定结肠上皮对HPD的反应。结果:HPD显著下调了与细胞代谢、NF-κ B B信号、DNA修复、谷胱甘肽代谢和细胞粘附相关的基因的表达。相反,HPD上调与细胞增殖和化学屏障功能相关的基因的表达。这些在mRNA水平上的变化与HPD对DNA完整性的不利影响无关(彗星试验),上皮更新(通过免疫组织化学和蛋白质印迹定量增殖和凋亡标志物)和结肠屏障完整性(Ussing chamber experiments). HPD后肠腔环境的改变与结肠内稳态的维持有关,这可能是适应性的结果。与观察到的转录调控相关的上皮细胞中的过程。
Background: High-protein diets (HPD) alter the large intestine microbiota composition in association with a metabolic shift towards protein degradation. Some amino acid-derived metabolites produced by the colon bacteria are beneficial for the mucosa while others are deleterious at high concentrations. The aim of the present work was to define the colonic epithelial response to an HPD. Transcriptome profiling was performed on colonocytes of rats fed an HPD or an isocaloric normal-protein diet (NPD) for 2 weeks.Results: The HPD downregulated the expression of genes notably implicated in pathways related to cellular metabolism, NF-kappa B signaling, DNA repair, glutathione metabolism and cellular adhesion in colonocytes. In contrast, the HPD upregulated the expression of genes related to cell proliferation and chemical barrier function. These changes at the mRNA level in colonocytes were not associated with detrimental effects of the HPD on DNA integrity (comet assay), epithelium renewal (quantification of proliferation and apoptosis markers by immunohistochemistry and western blot) and colonic barrier integrity (Ussing chamber experiments).Conclusion: The modifications of the luminal environment after an HPD were associated with maintenance of the colonic homeostasis that might be the result of adaptive processes in the epithelium related to the observed transcriptional regulations.