<br>B 型单端孢菌素霉菌毒素 Fusarenon-X 的肠道毒性：全转录组分析揭示了新的信号通路。,Scientific Reports

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B 型单端孢菌素霉菌毒素 Fusarenon-X 的肠道毒性：全转录组分析揭示了新的信号通路。
Scientific Reports ( IF 3.8 ) Pub Date : 2017-Aug-08 , DOI: 10.1038/s41598-017-07155-2
Imourana Alassane-Kpembi _{1,

2} , Juliana Rubira Gerez _{1,

3} , Anne-Marie Cossalter ₁ , Manon Neves ₁ , Joëlle Laffitte ₁ , Claire Naylies ₁ , Yannick Lippi ₁ , Martine Kolf-Clauw _{1,

4} , Ana Paula L Bracarense ₃ , Philippe Pinton ₁ , Isabelle P Oswald ₁

Affiliation

尽管初步结果表明 Fusarenon-X (FX) 的毒性比其他受管制的单端孢霉烯族化合物更高，但有关 fsarenon-X (FX) 的可用数据并不支持基于健康的指导值的推导。本研究旨在利用组织形态学分析和全转录组分析来全面了解 FX 引起的肠道变化。脱氧雪腐镰刀菌烯醇（DON）作为基准。 FX 比 DON 诱导更严重的组织学改变。炎症是两种霉菌毒素分子毒性的标志。 FX 上调关键炎症基因的基准剂量比之前报道的 DON 值高 4 至 45 倍。转录组分析显示，两种霉菌毒素均下调控制脂质代谢的过氧化物酶体增殖物激活受体 (PPAR) 和肝脏 X 受体 - 视黄醇 X 受体 (LXR-RXR) 信号通路。有趣的是，包括 VDR/RXR 激活、肝配蛋白受体信号传导和 GNRH 信号传导在内的多种途径是 FX 特有的，因此可以区分两种霉菌毒素的转录组指纹。这些结果表明 FX 比 DON 诱导更强烈的肠道炎症。此外，尽管两种霉菌毒素的毒性机制在许多方面相似，但本研究强调每种霉菌毒素针对的特定途径，强调需要对镰刀菌毒素进行基于特定机制的风险评估。

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

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.

更新日期：2017-08-08

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