Wen Yi, Rashid Faizan, Fazal Zeeshan, Singh Ratnakar, Spinella Michael J, Irudayaraj Joseph
Biomedical Research Center, Mills Breast Cancer Institute, Carle Foundation Hospital, 509 W University Ave, Urbana, IL 61801, USA.
Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, 2001 S Lincoln Ave, Urbana, IL 61801, USA.
Environ Epigenet. 2022 Apr 16;8(1):dvac010. doi: 10.1093/eep/dvac010. eCollection 2022.
Perfluorooctane sulfonate (PFOS) is a widespread persistent environmental pollutant implicated in nephrotoxicity with altered metabolism, carcinogenesis, and fibrosis potential. We studied the underlying epigenetic mechanism involving transcription factors of PFOS-induced kidney injury. A 14-day orally dosed mouse model was chosen to study acute influences . Messenger RNA expression analysis and gene set enrichment analysis were performed to elucidate the relationship between epigenetic regulators, transcription factors, kidney disease, and metabolism homeostasis. PFOS was found to accumulate in mouse kidney in a dose-dependent manner. Kidney injury markers and increased in expression significantly. Transcription factors, including , and were upregulated, while and were downregulated. Furthermore, global DNA methylation levels decreased and the gene expression of histone demethylases and were upregulated. Our work implicates PFOS-induced gene expression alterations in epigenetics, transcription factors, and kidney biomarkers with potential implications for kidney fibrosis and kidney carcinogenesis. Future experiments can focus on epigenetic mechanisms to establish a panel of PFOS-induced biomarkers for nephrotoxicity evaluation.
全氟辛烷磺酸（PFOS）是一种广泛存在的持久性环境污染物，与代谢改变、致癌作用以及潜在的纤维化相关的肾毒性有关。我们研究了涉及PFOS诱导的肾损伤转录因子的潜在表观遗传机制。选择一个为期14天的口服给药小鼠模型来研究急性影响。进行信使核糖核酸表达分析和基因集富集分析，以阐明表观遗传调节因子、转录因子、肾脏疾病和代谢稳态之间的关系。发现PFOS以剂量依赖的方式在小鼠肾脏中蓄积。肾脏损伤标志物和的表达显著增加。包括、和在内的转录因子上调，而和下调。此外，整体DNA甲基化水平降低，组蛋白去甲基化酶和的基因表达上调。我们的工作表明PFOS诱导的基因表达在表观遗传学、转录因子和肾脏生物标志物方面发生改变，对肾纤维化和肾癌发生具有潜在影响。未来的实验可以聚焦于表观遗传机制，以建立一组用于肾毒性评估的PFOS诱导生物标志物。
