Transcriptional and Proteomic Analysis Revealed a Synergistic Effect of Aflatoxin M1 and Ochratoxin A Mycotoxins on the Intestinal Epithelial Integrity of Differentiated Human Caco-2 Cells

文献类型： 外文期刊

第一作者： Gao, Yanan

作者： Gao, Yanan;Li, Songli;Bao, Xiaoyu;Luo, Chaochao;Yang, Huaigu;Wang, Jiaqi;Zhao, Shengguo;Zheng, Nan;Gao, Yanan;Li, Songli;Bao, Xiaoyu;Luo, Chaochao;Yang, Huaigu;Wang, Jiaqi;Zhao, Shengguo;Zheng, Nan;Gao, Yanan;Li, Songli;Bao, Xiaoyu;Luo, Chaochao;Yang, Huaigu;Wang, Jiaqi;Zhao, Shengguo;Zheng, Nan;Gao, Yanan;Li, Songli;Bao, Xiaoyu;Luo, Chaochao;Yang, Huaigu;Wang, Jiaqi;Zhao, Shengguo;Zheng, Nan

作者机构：

关键词： aflatoxin MI; ochratoxin A; omics; intestinal integrity; synergistic effect

期刊名称：JOURNAL OF PROTEOME RESEARCH （ 影响因子：4.466； 五年影响因子：4.352 ）

ISSN： 1535-3893

年卷期： 2018 年 17 卷 9 期

页码：

收录情况： SCI

摘要： Aflatoxin M1 (AFM1) is a common mycotoxin in dairy milk, and it is typically concurrently present with other mycotoxins that may represent a threat to food safety. However, knowledge of how AFM1, alone or in combination with other mycotoxins, may affect human intestinal epithelial integrity remain to be established. We employed transcriptome and proteome analysis integrated with biological validation to reveal the molecular basis underlining the effect of exposure to AFM1, ochratoxin A (OTA), or both on the intestinal epithelial integrity of differentiated Caco-2 cells. Exposure to 4 mu g/mL of OTA was found to disrupt human gut epithelial integrity, whereas 4 mu g/mL of AFM1 did not. The integrated transcriptome and proteome analysis of AFM1 and OTA, alone or in combination, indicate the synergistic effect of the two mycotoxins in disrupting intestinal integrity. This effect was mechanistically linked to a broad range of pathways related to intestinal integrity enriched by down-regulated genes and proteins, associated with focal adhesion, adheren junction, and gap junction pathways. Furthermore, the cross-omics analysis of mixed AFM1 and OTA compared to OTA alone suggest that kinase family members, including myosin light-chain kinase, mitogen-activated protein kinases, and protein kinase C, are the potential key regulators in modulating intestinal epithelial integrity. These findings provide novel insight into the synergistic detrimental role of multiple mycotoxins in disrupting intestinal integrity and, therefore, identify potential targets to improve milk safety related to human health.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序