Nephrotoxicity of perfluorooctane sulfonate (PFOS)—effect on transcription and epigenetic factors

Abstract

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 <i>in vivo</i>. 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 <i>Acta2</i> and <i>Bcl2l1</i> increased in expression significantly. Transcription factors, including <i>Nef2l2, Hes1, Ppara</i>, and <i>Ppard,</i> were upregulated, while <i>Smarca2</i> and <i>Pparg</i> were downregulated. Furthermore, global DNA methylation levels decreased and the gene expression of histone demethylases <i>Kdm1a</i> and <i>Kdm4c</i> 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.