Intestinal epithelial cell-specific restoration of Nrf2 gene in whole-body-knockout mice ameliorates acute colitis.

IF 2.2 4区 农林科学 Q1 VETERINARY SCIENCES Experimental Animals Pub Date : 2025-01-25 DOI:10.1538/expanim.24-0152
Tatsuhiro Sato, Keii To, Fumika Sakurai, Kanako Chihara, Eiji Warabi, Tomonori Isobe, Hideo Suzuki, Junichi Shoda, Kosuke Okada
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Abstract

Unbalanced redox homeostasis leads to the production of reactive oxygen species and exacerbates inflammatory bowel disease. To investigate the role of the transcription factor Nrf2, a major antioxidative stress sensor, in intestinal epithelial cells (IECs), we generated IEC-specific Nrf2 gene knock-in mice (Nrf2-vRes), which express Nrf2 only in IECs, using the cre/loxp system. Colitis was induced in wild-type (WT) mice, whole-body Nrf2-knockout (Nrf2-KO) mice, and Nrf2-vRes mice by administering dextran sulfate sodium (DSS) for 1 week (acute model) or intermittently for 5 weeks (chronic model). The mRNA and protein levels of NAD(P)H:quinone oxidoreductase 1 (NQO1), which is involved in the oxidative stress response in a manner regulated by Nrf2, were reduced in Nrf2-KO compared with those in WT, while these decreases were reversed in Nrf2-vRes at all timepoints. Nrf2-KO mice administered DSS developed more severe colitis with higher disease activity index, higher leucine-rich α2 glycoprotein in serum, shorter colon length, and more severe epithelial damage and infiltration of inflammatory cells histopathologically than did WT mice in the acute model; moreover, these exacerbations of colitis were ameliorated in Nrf2-vRes mice. However, these differences were not observed among the three sets of mice in the chronic model. IEC-specific expression of Nrf2 ameliorated DSS-induced acute colitis. These results suggest that Nrf2 expression in IECs plays a protective role against early-stage colitis and undertakes important regulatory functions during intestinal inflammation.

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来源期刊
Experimental Animals
Experimental Animals 生物-动物学
CiteScore
2.80
自引率
4.20%
发文量
2
审稿时长
3 months
期刊介绍: The aim of this international journal is to accelerate progress in laboratory animal experimentation and disseminate relevant information in related areas through publication of peer reviewed Original papers and Review articles. The journal covers basic to applied biomedical research centering around use of experimental animals and also covers topics related to experimental animals such as technology, management, and animal welfare.
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