L-Glutamate (Glu) is a nutritionally functional amino acid for pigs. In addition, intestinal stem cells (ISCs) maintain epithelial renewal and homeostasis by dynamically regulating proliferation and differentiation to cope with environmental cues. The rapid renewal of the intestinal epithelium requires a continuous supply of energy sources such as Glu. However, the effects of Glu on ISCs and epithelial renewal are poorly understood. In this study, we found that dietary Glu accelerated intestinal epithelial renewal and gut growth. The epidermal growth factor receptor (EGFR)/extracellular regulated protein kinase (ERK) pathway and mechanistic target of rapamycin complex 1 (mTORC1) signaling were involved in this response in piglets. Subsequent cellular assessment suggested that the EGFR/ERK pathway was upstream of Glu-induced mTORC1 signaling activation. Furthermore, we found that Glu activated the EGFR/ERK pathway and promoted ISC proliferation and differentiation in porcine intestinal organoids. Collectively, our findings suggest that Glu drives intestinal epithelial renewal by increasing ISC activity via the EGFR/ERK/mTORC1 pathway. The present study provides direct evidence that mTORC1 is activated by extracellular Glu through EGFR and that Glu acts as a nutritionally functional amino acid for piglets to maintain intestinal growth and health.

中文翻译：

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L-谷氨酸通过上调EGFR-ERK-mTORC1途径增加干细胞活性来驱动猪肠上皮更新

大号-谷氨酸（Glu）是猪的营养功能氨基酸。此外，肠道干细胞（ISC）通过动态调节增殖和分化以适应环境的提示来维持上皮更新和体内平衡。肠上皮的快速更新需要持续供应能源，例如Glu。但是，人们对Glu对ISC和上皮更新的影响知之甚少。在这项研究中，我们发现饮食中的Glu促进肠道上皮更新和肠道生长。表皮生长因子受体（EGFR）/细胞外调节蛋白激酶（ERK）途径和雷帕霉素复合物1（mTORC1）信号转导的机制靶点参与了仔猪的这种反应。随后的细胞评估表明，EGFR / ERK途径位于Glu诱导的mTORC1信号激活的上游。此外，我们发现Glu激活了猪肠类器官中的EGFR / ERK通路并促进了ISC增殖和分化。总的来说，我们的发现表明，Glu通过增加ISC活性来驱动肠上皮更新通过EGFR / ERK / mTORC1途径。本研究提供直接证据，证明mTORC1被EGFR的胞外Glu激活，并且Glu充当仔猪的营养功能氨基酸，以维持肠道生长和健康。