Integrative Transcriptomics Analysis Reveals Convergent Toxicological Effects of Perfluorooctanoic Acid and Perfluorooctane Sulfonate on Human Liver: Evidence from Multiple Models DOI Creative Commons
Renjun Yang, Nuoya Yin, Francesco Faiola

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: unknown, P. 138112 - 138112

Published: April 1, 2025

Perfluorooctanoic acid and perfluorooctane sulfonate are well-known eight-carbon per- polyfluoroalkyl substances (8C-PFAS) potentially toxic for the human liver. However, direct experimental evidence demonstrating their toxicity on liver remains limited. Consequently, this study aimed to extrapolate 8C-PFAS mechanisms by leveraging omics data integrate mouse findings. Through integration analyses of nine datasets (one human, six murine, two rat), we identified 199 genes with known biological functions that commonly affected across species. We delineated a comprehensive regulatory network toxicity, may trigger fatty disease up-regulating CD36 PPARα pathway; dysregulate xenobiotic metabolism disrupting CAR CYP family genes; induce cancer dysregulating WNT, TGFβ, FGF21, P53 pathways. also ATF3, EGR1, ESR1, NFATC4, SNAI2, TP53, EZH2 as transcriptionally regulated 8C-PFAS, along PPARα, RXRα, FGFR1, TCF3, SMAD3 functionally impacted. Collectively, these factors account over 90 % 8C-PFAS-affected key genes. This not only developed novel method extrapolating risks integrating scattered based transcriptomics data, but proposes new which contributes cancer.

Language: Английский

Integrative Transcriptomics Analysis Reveals Convergent Toxicological Effects of Perfluorooctanoic Acid and Perfluorooctane Sulfonate on Human Liver: Evidence from Multiple Models DOI Creative Commons
Renjun Yang, Nuoya Yin, Francesco Faiola

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: unknown, P. 138112 - 138112

Published: April 1, 2025

Perfluorooctanoic acid and perfluorooctane sulfonate are well-known eight-carbon per- polyfluoroalkyl substances (8C-PFAS) potentially toxic for the human liver. However, direct experimental evidence demonstrating their toxicity on liver remains limited. Consequently, this study aimed to extrapolate 8C-PFAS mechanisms by leveraging omics data integrate mouse findings. Through integration analyses of nine datasets (one human, six murine, two rat), we identified 199 genes with known biological functions that commonly affected across species. We delineated a comprehensive regulatory network toxicity, may trigger fatty disease up-regulating CD36 PPARα pathway; dysregulate xenobiotic metabolism disrupting CAR CYP family genes; induce cancer dysregulating WNT, TGFβ, FGF21, P53 pathways. also ATF3, EGR1, ESR1, NFATC4, SNAI2, TP53, EZH2 as transcriptionally regulated 8C-PFAS, along PPARα, RXRα, FGFR1, TCF3, SMAD3 functionally impacted. Collectively, these factors account over 90 % 8C-PFAS-affected key genes. This not only developed novel method extrapolating risks integrating scattered based transcriptomics data, but proposes new which contributes cancer.

Language: Английский

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