Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Int J Mol Sci. 2021 Dec 28;23(1):289. doi: 10.3390/ijms23010289.
Aflatoxin M1 (AFM1), the only toxin with maximum residue levels in milk, has adverse effects on the intestinal barrier, resulting in intestinal inflammatory disease. Lactoferrin (LF), one of the important bioactive proteins in milk, performs multiple biological functions, but knowledge of the protective effects of LF on the compromised intestinal barrier induced by AFM1 has not been investigated. In the present study, results using Balb/C mice and differentiated Caco-2 cells showed that LF intervention decreased AFM1-induced increased intestinal permeability, improved the protein expression of claudin-3, occludin and ZO-1, and repaired the injured intestinal barrier. The transcriptome and proteome were used to clarify the underlying mechanisms. It was found that LF reduced the intestinal barrier dysfunction caused by AFM1 and was associated with intestinal cell survival related pathways, such as cell cycle, apoptosis and MAPK signaling pathway and intestinal integrity related pathways including endocytosis, tight junction, adherens junction and gap junction. The cross-omics analysis suggested that insulin receptor (INSR), cytoplasmic FMR1 interacting protein 2 (CYFIP2), dedicator of cytokinesis 1 (DOCK1) and ribonucleotide reductase regulatory subunit M2 (RRM2) were the potential key regulators as LF repaired the compromised intestinal barrier. These findings indicated that LF may be an alternative treatment for the compromised intestinal barrier induced by AFM1.
黄曲霉毒素 M1（AFM1）是牛奶中唯一具有最大残留限量的毒素，对肠道屏障有不良影响，导致肠道炎症性疾病。乳铁蛋白（LF）是牛奶中重要的生物活性蛋白之一，具有多种生物学功能，但 LF 对 AFM1 引起的受损肠道屏障的保护作用尚未得到研究。本研究采用 Balb/C 小鼠和分化的 Caco-2 细胞进行研究，结果表明 LF 干预可降低 AFM1 诱导的肠道通透性增加，改善 claudin-3、occludin 和 ZO-1 的蛋白表达，修复受损的肠道屏障。转录组和蛋白质组用于阐明潜在的机制。结果发现 LF 减轻了 AFM1 引起的肠道屏障功能障碍，与细胞存活相关途径（如细胞周期、细胞凋亡和 MAPK 信号通路）和肠道完整性相关途径（包括内吞作用、紧密连接、黏着连接和间隙连接）有关。跨组学分析表明，胰岛素受体（INSR）、细胞质 FMR1 相互作用蛋白 2（CYFIP2）、胞质分裂器 1（DOCK1）和核苷酸还原酶调节亚基 M2（RRM2）可能是 LF 修复受损肠道屏障的潜在关键调节因子。这些发现表明 LF 可能是 AFM1 引起的受损肠道屏障的一种替代治疗方法。
