Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways

Abstract The few data available on fusarenon-X (FX) do not support the derivation of health-based guidance values, although preliminary results suggest higher toxicity than other regulated trichothecenes. Using histo-morphological analysis and whole transcriptome profiling, this study was designed t...

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Autores principales:	Imourana Alassane-Kpembi, Juliana Rubira Gerez, Anne-Marie Cossalter, Manon Neves, Joëlle Laffitte, Claire Naylies, Yannick Lippi, Martine Kolf-Clauw, Ana Paula L. Bracarense, Philippe Pinton, Isabelle P. Oswald
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7af54e295d7844b0bdaef1cb9f145286
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spelling	oai:doaj.org-article:7af54e295d7844b0bdaef1cb9f1452862021-12-02T16:06:50ZIntestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways10.1038/s41598-017-07155-22045-2322https://doaj.org/article/7af54e295d7844b0bdaef1cb9f1452862017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07155-2https://doaj.org/toc/2045-2322Abstract The few data available on fusarenon-X (FX) do not support the derivation of health-based guidance values, although preliminary results suggest higher toxicity than other regulated trichothecenes. Using histo-morphological analysis and whole transcriptome profiling, this study was designed to obtain a global view of the intestinal alterations induced by FX. Deoxynivalenol (DON) served as a benchmark. FX induced more severe histological alterations than DON. Inflammation was the hallmark of the molecular toxicity of both mycotoxins. The benchmark doses for the up-regulation of key inflammatory genes by FX were 4- to 45-fold higher than the previously reported values for DON. The transcriptome analysis revealed that both mycotoxins down-regulated the peroxisome proliferator-activated receptor (PPAR) and liver X receptor - retinoid X receptor (LXR-RXR) signaling pathways that control lipid metabolism. Interestingly, several pathways, including VDR/RXR activation, ephrin receptor signaling, and GNRH signaling, were specific to FX and thus discriminated the transcriptomic fingerprints of the two mycotoxins. These results demonstrate that FX induces more potent intestinal inflammation than DON. Moreover, although the mechanisms of toxicity of both mycotoxins are similar in many ways, this study emphasize specific pathways targeted by each mycotoxin, highlighting the need for specific mechanism-based risk assessments of Fusarium mycotoxins.Imourana Alassane-KpembiJuliana Rubira GerezAnne-Marie CossalterManon NevesJoëlle LaffitteClaire NayliesYannick LippiMartine Kolf-ClauwAna Paula L. BracarensePhilippe PintonIsabelle P. OswaldNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Imourana Alassane-Kpembi Juliana Rubira Gerez Anne-Marie Cossalter Manon Neves Joëlle Laffitte Claire Naylies Yannick Lippi Martine Kolf-Clauw Ana Paula L. Bracarense Philippe Pinton Isabelle P. Oswald Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways
description	Abstract The few data available on fusarenon-X (FX) do not support the derivation of health-based guidance values, although preliminary results suggest higher toxicity than other regulated trichothecenes. Using histo-morphological analysis and whole transcriptome profiling, this study was designed to obtain a global view of the intestinal alterations induced by FX. Deoxynivalenol (DON) served as a benchmark. FX induced more severe histological alterations than DON. Inflammation was the hallmark of the molecular toxicity of both mycotoxins. The benchmark doses for the up-regulation of key inflammatory genes by FX were 4- to 45-fold higher than the previously reported values for DON. The transcriptome analysis revealed that both mycotoxins down-regulated the peroxisome proliferator-activated receptor (PPAR) and liver X receptor - retinoid X receptor (LXR-RXR) signaling pathways that control lipid metabolism. Interestingly, several pathways, including VDR/RXR activation, ephrin receptor signaling, and GNRH signaling, were specific to FX and thus discriminated the transcriptomic fingerprints of the two mycotoxins. These results demonstrate that FX induces more potent intestinal inflammation than DON. Moreover, although the mechanisms of toxicity of both mycotoxins are similar in many ways, this study emphasize specific pathways targeted by each mycotoxin, highlighting the need for specific mechanism-based risk assessments of Fusarium mycotoxins.
format	article
author	Imourana Alassane-Kpembi Juliana Rubira Gerez Anne-Marie Cossalter Manon Neves Joëlle Laffitte Claire Naylies Yannick Lippi Martine Kolf-Clauw Ana Paula L. Bracarense Philippe Pinton Isabelle P. Oswald
author_facet	Imourana Alassane-Kpembi Juliana Rubira Gerez Anne-Marie Cossalter Manon Neves Joëlle Laffitte Claire Naylies Yannick Lippi Martine Kolf-Clauw Ana Paula L. Bracarense Philippe Pinton Isabelle P. Oswald
author_sort	Imourana Alassane-Kpembi
title	Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways
title_short	Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways
title_full	Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways
title_fullStr	Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways
title_full_unstemmed	Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways
title_sort	intestinal toxicity of the type b trichothecene mycotoxin fusarenon-x: whole transcriptome profiling reveals new signaling pathways
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7af54e295d7844b0bdaef1cb9f145286
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Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways

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