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Transcriptome and Metabolome Analyses Reveal Perfluorooctanoic Acid-Induced Kidney Injury by Interfering with PPAR Signaling Pathway

Perfluorooctanoic acid (PFOA) is widely used in aviation science and technology, transportation, electronics, kitchenware, and other household products. It is stable in the environment and has potential nephrotoxicity. To investigate the effect of PFOA exposure during pregnancy on the kidneys of off...

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Autores principales: Zhang, Yan, Li, Yang, Gao, Nana, Gong, Yinglan, Shi, Wanyu, Wang, Xiaodan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380573/
https://www.ncbi.nlm.nih.gov/pubmed/37511261
http://dx.doi.org/10.3390/ijms241411503
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author Zhang, Yan
Li, Yang
Gao, Nana
Gong, Yinglan
Shi, Wanyu
Wang, Xiaodan
author_facet Zhang, Yan
Li, Yang
Gao, Nana
Gong, Yinglan
Shi, Wanyu
Wang, Xiaodan
author_sort Zhang, Yan
collection PubMed
description Perfluorooctanoic acid (PFOA) is widely used in aviation science and technology, transportation, electronics, kitchenware, and other household products. It is stable in the environment and has potential nephrotoxicity. To investigate the effect of PFOA exposure during pregnancy on the kidneys of offspring mice, a total of 20 mice at day 0 of gestation were randomly divided into two groups (10 mice in each group), and each group was administered 0.2 mL of PFOA at a dose of 3.5 mg/kg or deionized water by gavage during gestation. The kidney weight, kidney index, histopathological observation, serum biochemistry, transcriptomics, and metabolomics of the kidneys of the 35-day offspring mice were analyzed. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels in the kidney were measured. Transcriptome analysis results showed that 387 genes were up-regulated and 283 genes were down-regulated compared with the control group. These differentially expressed genes (DEGs) were mainly concentrated in the peroxisome-proliferator-activated receptor (PPAR) signaling pathway and circadian rhythm. Compared with the control group, 64 and 73 metabolites were up- and down-regulated, respectively, in the PFOA group. The altered metabolites were mainly enriched in the biosynthesis of unsaturated fatty acids. PFOA can affect the expression levels of circadian rhythm-related genes in the kidneys of offspring mice, and this change is influenced by the PPAR signaling pathway. PFOA causes oxidative stress in the kidneys, which is responsible for significant changes in metabolites associated with the biosynthesis of unsaturated fatty acids.
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spelling pubmed-103805732023-07-29 Transcriptome and Metabolome Analyses Reveal Perfluorooctanoic Acid-Induced Kidney Injury by Interfering with PPAR Signaling Pathway Zhang, Yan Li, Yang Gao, Nana Gong, Yinglan Shi, Wanyu Wang, Xiaodan Int J Mol Sci Article Perfluorooctanoic acid (PFOA) is widely used in aviation science and technology, transportation, electronics, kitchenware, and other household products. It is stable in the environment and has potential nephrotoxicity. To investigate the effect of PFOA exposure during pregnancy on the kidneys of offspring mice, a total of 20 mice at day 0 of gestation were randomly divided into two groups (10 mice in each group), and each group was administered 0.2 mL of PFOA at a dose of 3.5 mg/kg or deionized water by gavage during gestation. The kidney weight, kidney index, histopathological observation, serum biochemistry, transcriptomics, and metabolomics of the kidneys of the 35-day offspring mice were analyzed. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels in the kidney were measured. Transcriptome analysis results showed that 387 genes were up-regulated and 283 genes were down-regulated compared with the control group. These differentially expressed genes (DEGs) were mainly concentrated in the peroxisome-proliferator-activated receptor (PPAR) signaling pathway and circadian rhythm. Compared with the control group, 64 and 73 metabolites were up- and down-regulated, respectively, in the PFOA group. The altered metabolites were mainly enriched in the biosynthesis of unsaturated fatty acids. PFOA can affect the expression levels of circadian rhythm-related genes in the kidneys of offspring mice, and this change is influenced by the PPAR signaling pathway. PFOA causes oxidative stress in the kidneys, which is responsible for significant changes in metabolites associated with the biosynthesis of unsaturated fatty acids. MDPI 2023-07-15 /pmc/articles/PMC10380573/ /pubmed/37511261 http://dx.doi.org/10.3390/ijms241411503 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Yan
Li, Yang
Gao, Nana
Gong, Yinglan
Shi, Wanyu
Wang, Xiaodan
Transcriptome and Metabolome Analyses Reveal Perfluorooctanoic Acid-Induced Kidney Injury by Interfering with PPAR Signaling Pathway
title Transcriptome and Metabolome Analyses Reveal Perfluorooctanoic Acid-Induced Kidney Injury by Interfering with PPAR Signaling Pathway
title_full Transcriptome and Metabolome Analyses Reveal Perfluorooctanoic Acid-Induced Kidney Injury by Interfering with PPAR Signaling Pathway
title_fullStr Transcriptome and Metabolome Analyses Reveal Perfluorooctanoic Acid-Induced Kidney Injury by Interfering with PPAR Signaling Pathway
title_full_unstemmed Transcriptome and Metabolome Analyses Reveal Perfluorooctanoic Acid-Induced Kidney Injury by Interfering with PPAR Signaling Pathway
title_short Transcriptome and Metabolome Analyses Reveal Perfluorooctanoic Acid-Induced Kidney Injury by Interfering with PPAR Signaling Pathway
title_sort transcriptome and metabolome analyses reveal perfluorooctanoic acid-induced kidney injury by interfering with ppar signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380573/
https://www.ncbi.nlm.nih.gov/pubmed/37511261
http://dx.doi.org/10.3390/ijms241411503
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