表观遗传学
DNA甲基化
生物
转录因子
肾毒性
全氟辛烷
基因表达
肾
肾脏疾病
癌症研究
化学
内分泌学
遗传学
基因
钠
磺酸盐
有机化学
作者
Yi Wen,Faizan Rashid,Zeeshan Fazal,Ratnakar Singh,Michael J. Spinella,Joseph Irudayaraj
出处
期刊:Current Zoology
[Oxford University Press]
日期:2022-01-01
卷期号:8 (1)
被引量:10
摘要
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 in vivo. 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 Acta2 and Bcl2l1 increased in expression significantly. Transcription factors, including Nef2l2, Hes1, Ppara, and Ppard, were upregulated, while Smarca2 and Pparg were downregulated. Furthermore, global DNA methylation levels decreased and the gene expression of histone demethylases Kdm1a and Kdm4c 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.
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