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