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ACE2 通过修复涉及 mTOR 途径的肠屏障来介导色氨酸缓解腹泻。

ACE2 mediates tryptophan alleviation on diarrhea by repairing intestine barrier involved mTOR pathway.

机构信息

State Key Laboratory of Swine and Poultry Breeding Industry and Guangdong Provincial Key Laboratory of Animal Nutrition and Regulation, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.

Zhuhai Tianjiao Technology Co., LTD, Zhuhai, 519000, China.

出版信息

Cell Mol Biol Lett. 2024 Jun 14;29(1):90. doi: 10.1186/s11658-024-00603-8.


DOI:10.1186/s11658-024-00603-8
PMID:38877403
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11179371/
Abstract

The membrane-delimited receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2 (ACE2), which is expressed in the intestine, collaborates with broad neutral amino acid transporter 1 (BAT1). Tryptophan (Trp) is transported into intestinal epithelial cells by ACE2 and BAT1. However, whether ACE2 and its binding protein BAT1 are involved in Trp-mediated alleviation of intestinal injury is largely unknown. Here, we used weaned piglets and IPEC-J2 cells as models and found that ACE2/BAT1 alleviated lipopolysaccharide (LPS)-induced diarrhea and promoted intestinal barrier recovery via transport of Trp. The levels of the aryl hydrocarbon receptor (AhR) and mechanistic target of rapamycin (mTOR) pathways were altered by ACE2. Dietary Trp supplementation in LPS-treated weaned piglets revealed that Trp alleviated diarrhea by promoting ACE2/BAT1 expression, and examination of intestinal morphology revealed that the damage to the intestinal barrier was repaired. Our study demonstrated that ACE2 accompanied by BAT1 mediated the alleviation of diarrhea by Trp through intestinal barrier repair via the mTOR pathway.

摘要

严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的膜限受体血管紧张素转换酶 2(ACE2)在肠道中表达,它与广泛的中性氨基酸转运蛋白 1(BAT1)合作。色氨酸(Trp)通过 ACE2 和 BAT1 被转运到肠道上皮细胞内。然而,ACE2 及其结合蛋白 BAT1 是否参与 Trp 介导的缓解肠道损伤在很大程度上尚不清楚。在这里,我们使用断奶仔猪和 IPEC-J2 细胞作为模型,发现 ACE2/BAT1 通过转运 Trp 缓解了脂多糖(LPS)诱导的腹泻并促进了肠道屏障的恢复。ACE2 改变了芳香烃受体(AhR)和雷帕霉素(mTOR)途径的机制靶点。在 LPS 处理的断奶仔猪中补充膳食 Trp 表明,Trp 通过促进 ACE2/BAT1 的表达来缓解腹泻,并且对肠道形态的检查表明肠道屏障的损伤得到了修复。我们的研究表明,ACE2 伴随着 BAT1 通过 mTOR 途径介导了 Trp 通过肠道屏障修复来缓解腹泻。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/b8b686d15570/11658_2024_603_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/cbe5cfbfc86e/11658_2024_603_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/da566ee93df7/11658_2024_603_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/ea9c07c4d4cc/11658_2024_603_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/30fc43b9f21b/11658_2024_603_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/f32492d4a3c4/11658_2024_603_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/fd5f28b95e6d/11658_2024_603_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/b8b686d15570/11658_2024_603_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/cbe5cfbfc86e/11658_2024_603_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/da566ee93df7/11658_2024_603_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/ea9c07c4d4cc/11658_2024_603_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/30fc43b9f21b/11658_2024_603_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/f32492d4a3c4/11658_2024_603_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/fd5f28b95e6d/11658_2024_603_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ed/11179371/b8b686d15570/11658_2024_603_Fig7_HTML.jpg

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引用本文的文献

[1]
Advances in gut-lung axis research: clinical perspectives on pneumonia prevention and treatment.

Front Immunol. 2025-4-22

[2]
Cow Placenta Peptides Ameliorate D-Galactose-Induced Intestinal Barrier Damage by Regulating TLR/NF-κB Pathway.

Vet Sci. 2025-3-3

[3]
Heat Stress in Growing-Finishing Pigs: Effects of Low Protein with Increased Crystalline Amino Acids on Growth, Gut Health, Antioxidant Status and Microbiome.

Animals (Basel). 2025-3-15

[4]
Role of Kynurenine and Its Derivatives in Liver Diseases: Recent Advances and Future Clinical Perspectives.

Int J Mol Sci. 2025-1-24

[5]
Microbiota-derived tryptophan metabolism and AMPK/mTOR pathway mediate antidepressant-like effect of Shugan Hewei Decoction.

Front Pharmacol. 2024-9-16

本文引用的文献

[1]
Food science and COVID-19.

Food Sci Hum Wellness. 2021-1

[2]
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Cell Metab. 2022-11-1

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Q Rev Biophys. 2022-8-18

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Tryptophan Supplementation Enhances Intestinal Health by Improving Gut Barrier Function, Alleviating Inflammation, and Modulating Intestinal Microbiome in Lipopolysaccharide-Challenged Piglets.

Front Microbiol. 2022-7-4

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Butyrate, a typical product of gut microbiome, affects function of the AhR gene, being a possible agent of crosstalk between gut microbiome, and hepatic drug metabolism.

J Nutr Biochem. 2022-9

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Cell-intrinsic Aryl Hydrocarbon Receptor signalling is required for the resolution of injury-induced colonic stem cells.

Nat Commun. 2022-4-5

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Tryptophan Promotes Intestinal Immune Defense through Calcium-Sensing Receptor (CaSR)-Dependent Metabolic Pathways.

J Agric Food Chem. 2021-11-17

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