{"title":"Identification and functional analysis of hub genes involved in deoxynivalenol-induced enterotoxicity in porcine (Sus scrofa).","authors":"Jinhua He, Geng Zhao, Mingxia Chen, Ximing Ren, Peizhi Zhu, Zhizhong Liu, Jiayi Zhou, Hanwei Chen, Chuqiao Xiao, Xiang-Guang Li","doi":"10.1016/j.ecoenv.2024.117544","DOIUrl":null,"url":null,"abstract":"<p><p>Deoxynivalenol (DON) is a type of mycotoxin commonly found in food and animal feed. When consumed, it can have harmful effects on the intestine. The porcine digestive system is physiologically similar to that of humans, making pigs a suitable model for studying DON-induced enterotoxicity. However, the exact ways DON causes intestinal damage in pigs still need to be fully understood. To address this knowledge gap, this study aimed to identify hub genes associated with enterotoxicity caused by DON exposure. Transcriptomic datasets from porcine jejunal explants exposed to DON were extensively analyzed using bioinformatic techniques in this study. A total of 265 differentially expressed genes (DEGs) were identified, with 238 being up-regulated and 27 being down-regulated, indicating that exposure to DON tends to increase gene expression. Further analysis revealed that the up-regulated DEGs were enriched in tumor necrosis factor, nuclear factor kappa-B, mitogen-activated protein kinases, and Janus kinase/signal transducer and activator of transcription-related signaling pathways. In addition, Weighted gene co-expression network analysis was performed to identify highly co-expressed modules. Then, genes in the highest co-expressed module were intersected with the up-regulated DEGs to construct a Protein-Protein Interaction network, resulting in 237 overlapping genes. Subsequently, 6 hub genes (CXCR4, PTGS2, ICAM1, IL-1A, IL-1B, and IL-10) that played a central role in the response to DON were identified using cytohubba in conjunction with the Molecular Complex Detection. In summary, exposure to DON is more likely to result in increased rather than decreased gene expression. Six of the upregulated genes, which are involved in immunoregulation and inflammation, were identified as hub genes related to DON-induced enterotoxicity in pigs. This study provides new insights into the mechanisms underlying DON-induced enterotoxicity and could guide interventions for this condition.</p>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"290 ","pages":"117544"},"PeriodicalIF":6.2000,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ecotoxicology and Environmental Safety","FirstCategoryId":"93","ListUrlMain":"https://doi.org/10.1016/j.ecoenv.2024.117544","RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Deoxynivalenol (DON) is a type of mycotoxin commonly found in food and animal feed. When consumed, it can have harmful effects on the intestine. The porcine digestive system is physiologically similar to that of humans, making pigs a suitable model for studying DON-induced enterotoxicity. However, the exact ways DON causes intestinal damage in pigs still need to be fully understood. To address this knowledge gap, this study aimed to identify hub genes associated with enterotoxicity caused by DON exposure. Transcriptomic datasets from porcine jejunal explants exposed to DON were extensively analyzed using bioinformatic techniques in this study. A total of 265 differentially expressed genes (DEGs) were identified, with 238 being up-regulated and 27 being down-regulated, indicating that exposure to DON tends to increase gene expression. Further analysis revealed that the up-regulated DEGs were enriched in tumor necrosis factor, nuclear factor kappa-B, mitogen-activated protein kinases, and Janus kinase/signal transducer and activator of transcription-related signaling pathways. In addition, Weighted gene co-expression network analysis was performed to identify highly co-expressed modules. Then, genes in the highest co-expressed module were intersected with the up-regulated DEGs to construct a Protein-Protein Interaction network, resulting in 237 overlapping genes. Subsequently, 6 hub genes (CXCR4, PTGS2, ICAM1, IL-1A, IL-1B, and IL-10) that played a central role in the response to DON were identified using cytohubba in conjunction with the Molecular Complex Detection. In summary, exposure to DON is more likely to result in increased rather than decreased gene expression. Six of the upregulated genes, which are involved in immunoregulation and inflammation, were identified as hub genes related to DON-induced enterotoxicity in pigs. This study provides new insights into the mechanisms underlying DON-induced enterotoxicity and could guide interventions for this condition.
脱氧雪腐镰刀菌烯醇(DON)是一种霉菌毒素,常见于食品和动物饲料中。食用后会对肠道产生有害影响。猪的消化系统在生理上与人类相似,因此猪是研究 DON 引起的肠毒性的合适模型。然而,DON 对猪造成肠道损伤的确切方式仍有待充分了解。为了填补这一知识空白,本研究旨在确定与 DON 暴露引起的肠毒性相关的枢纽基因。本研究使用生物信息学技术广泛分析了暴露于 DON 的猪空肠外植体的转录组数据集。共鉴定出 265 个差异表达基因(DEGs),其中 238 个基因上调,27 个基因下调,表明暴露于 DON 会增加基因的表达。进一步分析发现,上调的 DEGs 富集于肿瘤坏死因子、核因子 kappa-B、丝裂原活化蛋白激酶和 Janus 激酶/信号转导和转录激活因子相关的信号通路。此外,还进行了加权基因共表达网络分析,以确定高共表达模块。然后,将共表达最高的模块中的基因与上调的 DEGs 相交,构建蛋白-蛋白相互作用网络,得出 237 个重叠基因。随后,利用 cytohubba 与分子复合体检测相结合,确定了在对 DON 的反应中起核心作用的 6 个中心基因(CXCR4、PTGS2、ICAM1、IL-1A、IL-1B 和 IL-10)。总之,暴露于 DON 更有可能导致基因表达的增加而不是减少。在上调的基因中,有六个参与免疫调节和炎症的基因被确定为与 DON 诱导的猪肠毒性有关的枢纽基因。这项研究为了解 DON 诱导的肠毒性的机制提供了新的视角,并可为干预这种疾病提供指导。
期刊介绍:
Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.