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玉米赤霉烯酮暴露破坏大鼠结肠中的 STAT-ISG15:玉米赤霉烯酮与炎症性肠病之间的潜在联系。

Zearalenone Exposure Disrupts STAT-ISG15 in Rat Colon: A Potential Linkage between Zearalenone and Inflammatory Bowel Disease.

机构信息

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.

Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100091, China.

出版信息

Toxins (Basel). 2023 Jun 9;15(6):392. doi: 10.3390/toxins15060392.

Abstract

Zearalenone (ZEN), a prevalent mycotoxin contaminating food and known for its intestinal toxicity, has been suggested as a potential risk factor for inflammatory bowel disease (IBD), although the exact relationship between ZEN exposure and IBD remains unclear. In this study, we established a rat model of colon toxicity induced by ZEN exposure to investigate the key targets of ZEN-induced colon toxicity and explore the underlying connection between ZEN exposure and IBD. Histological staining of the rat colon revealed significant pathological changes resulting from ZEN exposure ( < 0.01). Furthermore, the proteomic analysis demonstrated a notable upregulation of protein expression levels, specifically STAT2 (0.12 ± 0.0186), STAT6 (0.36 ± 0.0475) and ISG15 (0.43 ± 0.0226) in the rat colon ( < 0.05). Utilizing bioinformatics analysis, we combined ZEN exposure and IBD clinical sample databases to reveal that ZEN exposure may increase the risk of IBD through activation of the STAT-ISG15 pathway. This study identified novel targets for ZEN-induced intestinal toxicity, providing the basis for further study of ZEN exposure to IBD.

摘要

玉米赤霉烯酮(ZEN)是一种普遍存在的食物真菌毒素,其具有肠道毒性,被认为是炎症性肠病(IBD)的潜在危险因素,尽管 ZEN 暴露与 IBD 的确切关系仍不清楚。在这项研究中,我们建立了 ZEN 暴露诱导的大鼠结肠毒性模型,以研究 ZEN 诱导的结肠毒性的关键靶点,并探讨 ZEN 暴露与 IBD 之间的潜在联系。大鼠结肠的组织学染色显示 ZEN 暴露引起的显著病理变化(<0.01)。此外,蛋白质组学分析表明,大鼠结肠中 STAT2(0.12±0.0186)、STAT6(0.36±0.0475)和 ISG15(0.43±0.0226)的蛋白表达水平显著上调(<0.05)。利用生物信息学分析,我们将 ZEN 暴露和 IBD 临床样本数据库相结合,发现 ZEN 暴露可能通过激活 STAT-ISG15 通路增加 IBD 的风险。这项研究确定了 ZEN 诱导的肠道毒性的新靶点,为进一步研究 ZEN 暴露与 IBD 提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b43/10304514/53efb3efe5fb/toxins-15-00392-g001.jpg

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