黄曲霉毒素B1(AFB1)不仅在畜牧业生产中造成重大损失,而且对人类健康构成严重威胁。它是已知化学物质中最具致癌性的。猪对AFB1更敏感,发病率更高。然而,AFB1毒性作用的分子机制尚不清楚。在这项研究中,我们使用测序(ATAC-seq)和RNA-seq对转座酶可接近的染色质进行测定,以揭示早期暴露于AFB1期间PK-15细胞中染色质可接近性和基因表达动力学.我们观察到AFB1的毒性作用涉及p53、PI3K-AKT等信号通路,河马,MAPK,TLRs,凋亡,自噬,和癌症途径。碱性亮氨酸拉链(bZIP)转录因子(TFs),包括AP-1,Fos,JunB,Fra2在调节AFB1挑战中涉及的生物过程中起着至关重要的作用。几个新的TFs,比如Boris,HNF1b,Atf1和KNRNPH2代表AFB1毒性机制的潜在靶标。此外,关注细胞内锌离子的浓度是至关重要的。这些发现将有助于更好地理解AFB1诱导的肾毒性的机制,并提供新的分子靶标。
Aflatoxin B1 (AFB1) not only causes significant losses in livestock production but also poses a serious threat to human health. It is the most carcinogenic among known chemicals. Pigs are more susceptible to AFB1 and experience a higher incidence. However, the molecular mechanism of the toxic effect of AFB1 remains unclear. In this study, we used assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA-seq to uncover chromatin accessibility and gene expression dynamics in PK-15 cells during early exposure to AFB1. We observed that the toxic effects of AFB1 involve signaling pathways such as p53, PI3K-AKT, Hippo, MAPK, TLRs, apoptosis, autophagy, and cancer pathways. Basic leucine zipper (bZIP) transcription factors (TFs), including AP-1, Fos, JunB, and Fra2, play a crucial role in regulating the biological processes involved in AFB1 challenge. Several new TFs, such as BORIS, HNF1b, Atf1, and KNRNPH2, represent potential targets for the toxic mechanism of AFB1. In addition, it is crucial to focus on the concentration of intracellular zinc ions. These findings will contribute to a better understanding of the mechanisms underlying AFB1-induced nephrotoxicity and offer new molecular targets.