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铁对哺乳期仔猪肠道上皮发育的作用机制。

Mechanism of iron on the intestinal epithelium development in suckling piglets.

机构信息

Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.

Key Laboratory of Agro-ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China.

出版信息

Sci China Life Sci. 2023 Sep;66(9):2070-2085. doi: 10.1007/s11427-022-2307-7. Epub 2023 May 18.

Abstract

This study aimed to investigate the mechanism of iron on intestinal epithelium development of suckling piglets. Compared with newborn piglets, 7-day-old and 21-day-old piglets showed changes in the morphology of the jejunum, increased proliferation, differentiated epithelial cells, and expanded enteroids. Intestinal epithelium maturation markers and iron metabolism genes were significantly changed. These results suggest that lactation is a critical stage in intestinal epithelial development, accompanied by changes in iron metabolism. In addition, deferoxamine (DFO) treatment inhibited the activity of intestinal organoids at passage 4 (P4) of 0-day-old piglets, but no significant difference was observed in epithelial maturation markers at passage 1 (P1) and P4, and only argininosuccinate synthetase 1 (Ass1) and β-galactosidase (Gleb) were up-regulated at passage 7 (P7). These results in vitro show that iron deficiency may not directly affect intestinal epithelium development through intestinal stem cells (ISCs). The iron supplementation significantly down-regulated the mRNA expression of interleukin-22 receptor subunit alpha-2 (IL-22RA2) in the jejunum of piglets. Furthermore, the mRNA expression of IL-22 in 7-day-old piglets was significantly higher than that in 0-day-old piglets. Adult epithelial markers were significantly up-regulated in organoids treated with recombinant murine cytokine IL-22. Thus, IL-22 may play a key role in iron-affecting intestinal epithelium development.

摘要

本研究旨在探讨铁对哺乳期仔猪肠道上皮发育的作用机制。与新生仔猪相比,7 日龄和 21 日龄仔猪空肠形态发生变化,增殖增加,分化的上皮细胞增多,类器官扩大。肠上皮成熟标志物和铁代谢基因明显改变。这些结果表明,哺乳期是肠道上皮发育的关键阶段,伴随着铁代谢的变化。此外,去铁胺(DFO)处理抑制了 0 日龄仔猪第 4 代(P4)肠类器官的活性,但在第 1 代(P1)和 P4 时上皮成熟标志物无显著差异,仅第 7 代(P7)时精氨酸合成酶 1(Ass1)和β-半乳糖苷酶(Gleb)上调。这些体外结果表明,铁缺乏可能不会通过肠干细胞(ISCs)直接影响肠道上皮发育。铁补充显著下调了仔猪空肠中白细胞介素-22 受体亚单位α-2(IL-22RA2)的 mRNA 表达。此外,7 日龄仔猪的 IL-22mRNA 表达明显高于 0 日龄仔猪。用重组鼠细胞因子 IL-22 处理的类器官中,成年上皮标志物的 mRNA 表达显著上调。因此,IL-22 可能在铁影响肠道上皮发育中发挥关键作用。

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