National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, PR. China.
National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, PR. China.
Aquat Toxicol. 2023 May;258:106514. doi: 10.1016/j.aquatox.2023.106514. Epub 2023 Mar 31.
Previous studies have confirmed that bisphenol A (BPA) induced immune toxicity and affected diseases, however, the underlying mechanism remains unknown. In the present study, zebrafish was employed as the model to assess the immunotoxicity and the potential disease risk of BPA exposure. Upon BPA exposure, a series of abnormalities were found, which included the increased oxidative stress, damaged innate and adaptive immune functions and the elevated insulin and blood glucose levels. According to the target prediction and RNA sequencing data of BPA, the differential expression genes were found enriched in immune- and pancreatic cancer-related pathway and process, and the potential role of stat3 in the regulation of these processes was revealed. The key immune- and pancreatic cancer-related genes were selected for further confirmation by RT-qPCR. Based on the changes in the expression levels of these genes, our hypothesis that BPA induced the occurrence of pancreatic cancer by modulating immune responses was further evidenced. Deeper mechanism was further disclosed by molecular dock simulation and survival analysis of key genes, proving that BPA stably bound to STAT3 and IL10 and STAT3 may serve as the target of BPA-inducing pancreatic cancer. These results are of great significance in deepening the molecular mechanism of immunotoxicity induced by BPA and our understanding of the risk assessment of contaminants.
先前的研究已经证实双酚 A（BPA）会引起免疫毒性并影响疾病，但其中的具体机制仍不清楚。在本研究中，我们以斑马鱼为模型来评估 BPA 暴露的免疫毒性及其潜在的疾病风险。在 BPA 暴露后，我们发现了一系列异常，包括氧化应激增加、先天和适应性免疫功能受损以及胰岛素和血糖水平升高。根据 BPA 的靶标预测和 RNA 测序数据，我们发现差异表达基因富集在免疫和胰腺癌相关通路和过程中，并揭示了 stat3 在调节这些过程中的潜在作用。我们选择了关键的免疫和胰腺癌相关基因，通过 RT-qPCR 进一步验证。基于这些基因表达水平的变化，我们的假设得到了进一步证实，即 BPA 通过调节免疫反应引起胰腺癌的发生。通过对关键基因的分子对接模拟和生存分析，进一步揭示了更深层次的机制，证明 BPA 能稳定地与 STAT3 和 IL10 结合，STAT3 可能是 BPA 诱导胰腺癌的靶标。这些结果对于深入了解 BPA 引起的免疫毒性的分子机制以及我们对污染物风险评估的理解具有重要意义。
