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培养的人软骨细胞暴露于T-2毒素和脱氧雪腐镰刀菌烯醇的基因表达谱及分子机制

Gene expression profiles and molecular mechanism of cultured human chondrocytes' exposure to T-2 toxin and deoxynivalenol.

作者信息

Yang Lei, Zhang Jianping, Zhao Guanghui, Wu Cuiyan, Ning Yujie, Wang Xi, Lammi Mikko J, Guo Xiong

机构信息

School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Xi'an 710061, Shaanxi, PR China.

School of Clinical Medicine, Hainan Medical University, Haikou 571199, Hainan, PR China.

出版信息

Toxicon. 2017 Dec 15;140:38-44. doi: 10.1016/j.toxicon.2017.06.014. Epub 2017 Jul 3.

Abstract

T-2 toxin and deoxynivalenol (DON) are secondary metabolites produced by Fusarium fungi and are commonly found on food and feed. Although T-2 toxin and DON have been suggested as the etiology of Kashin-Beck disease (KBD), an endemic osteochondropathy, little is known about the mechanism when human chondrocytes are exposed to T-2 toxin and DON. The purpose of this study is to identify the gene expression differences and underlying molecular changes modulated by T-2 toxin and DON in vitro in human chondrocytes. After the experiments of cell viability, the gene expression profiles were analyzed in cells that were treated with 0.01 μg/ml T-2 toxin and 1.0 μg/ml DON for 72 h by Affymetrix Human Gene Chip. The array results showed that 882 and 2118 genes were differentially expressed for T-2 toxin and DON exposure, respectively. Enrichment analysis revealed that diverse cellular processes including DNA damage, cell cycle regulation and metabolism of extracellular matrix were affected when human chondrocytes were exposed to T-2 toxin and DON. These results demonstrate the gene expression differences and molecular mechanism of cultured human chondrocytes exposure to T-2 toxin and DON, and provide a new insight into future research in the etiology of KBD.

摘要

T-2毒素和脱氧雪腐镰刀菌烯醇(DON)是镰刀菌产生的次生代谢产物,常见于食品和饲料中。尽管T-2毒素和DON被认为是大骨节病(一种地方性骨软骨病)的病因,但对于人类软骨细胞暴露于T-2毒素和DON时的机制知之甚少。本研究的目的是确定T-2毒素和DON在体外对人类软骨细胞基因表达的差异及潜在的分子变化。在细胞活力实验后,使用Affymetrix人类基因芯片分析了用0.01μg/ml T-2毒素和1.0μg/ml DON处理72小时的细胞的基因表达谱。阵列结果显示,T-2毒素和DON暴露分别导致882个和2118个基因差异表达。富集分析表明,当人类软骨细胞暴露于T-2毒素和DON时,包括DNA损伤、细胞周期调控和细胞外基质代谢在内的多种细胞过程受到影响。这些结果证明了培养的人类软骨细胞暴露于T-2毒素和DON时的基因表达差异和分子机制,并为大骨节病病因的未来研究提供了新的见解。

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