• 中文核心期刊要目总览
  • 中国科技核心期刊
  • 中国科学引文数据库(CSCD)
  • 中国科技论文与引文数据库(CSTPCD)
  • 中国学术期刊文摘数据库(CSAD)
  • 中国学术期刊(网络版)(CNKI)
  • 中文科技期刊数据库
  • 万方数据知识服务平台
  • 中国超星期刊域出版平台
  • 国家科技学术期刊开放平台
  • 荷兰文摘与引文数据库(SCOPUS)
  • 日本科学技术振兴机构数据库(JST)
任艺, 刘水芳, 聂力, 蔡时煜, 陈炯. 2019: 香鱼NOD2在活化NF-κB和MAPK信号通路及抗细菌先天免疫中的功能研究. 动物学研究, 40(2): 77-88. DOI: 10.24272/j.issn.2095-8137.2018.066
引用本文: 任艺, 刘水芳, 聂力, 蔡时煜, 陈炯. 2019: 香鱼NOD2在活化NF-κB和MAPK信号通路及抗细菌先天免疫中的功能研究. 动物学研究, 40(2): 77-88. DOI: 10.24272/j.issn.2095-8137.2018.066
Yi Ren, Shui-Fang Liu, Li Nie, Shi-Yu Cai, Jiong Chen. 2019: Involvement of ayu NOD2 in NF-κB and MAPK signaling pathways: Insights into functional conservation of NOD2 in antibacterial innate immunity. Zoological Research, 40(2): 77-88. DOI: 10.24272/j.issn.2095-8137.2018.066
Citation: Yi Ren, Shui-Fang Liu, Li Nie, Shi-Yu Cai, Jiong Chen. 2019: Involvement of ayu NOD2 in NF-κB and MAPK signaling pathways: Insights into functional conservation of NOD2 in antibacterial innate immunity. Zoological Research, 40(2): 77-88. DOI: 10.24272/j.issn.2095-8137.2018.066

香鱼NOD2在活化NF-κB和MAPK信号通路及抗细菌先天免疫中的功能研究

Involvement of ayu NOD2 in NF-κB and MAPK signaling pathways: Insights into functional conservation of NOD2 in antibacterial innate immunity

  • 摘要: NOD样受体2(NOD2)是胞质重要的模式识别受体,在清除哺乳动物细胞质中细菌的过程中起到重要作用。然而,关于硬骨鱼类NOD2激活的信号通路研究罕有报道。因此,本研究拟在香鱼中鉴定一个NOD2受体的同源分子,并命名为PaNOD2。生物信息学分析显示,NOD2蛋白在脊椎动物进化过程中高度保守。功能研究发现,香鱼NOD2与其哺乳动物中的同源物一样,通过LRR结构域识别并结合细菌细胞壁组分胞壁酰二肽。在HEK293T和香鱼头肾巨噬细胞中过表达PaNOD2能够激活NF-κB信号通路,进而诱导炎症因子如PaTNF-α和PaIL-1β的mRNA表达。此外,在硬骨鱼中首次发现过表达PaNOD2同时能激活MAP激酶信号通路,催化p-38、Erk1/2和 JNK1/2的磷酸化。本研究探索了PaNOD2的分子结构及其活化的信号通路;证明了该分子在硬骨鱼至哺乳动物的进化过程中高度保守。因此,香鱼可以作为后续研究基于NOD2的病变及治疗方法的动物模型。

     

    Abstract: Nucleotide oligomerization domain 2 (NOD2) is a major cytoplasmic sensor for pathogens and is critical for the clearance of cytosolic bacteria in mammals. However, studies regarding NOD2, especially the initiated signaling pathways, are scarce in teleost species. In this study, we identified a NOD2 molecule (PaNOD2) from ayu (Plecoglossus altivelis). Bioinformatics analysis showed the structure of NOD2 to be highly conserved during vertebrate evolution. Dual-luciferase reporter assays examined the activation of NF-κB signaling and Western blotting analysis detected the phosphorylation of three MAP kinases (p-38, Erk1/2, and JNK1/2). Functional study revealed that, like its mammalian counterparts, PaNOD2 was the receptor of the bacterial cell wall component muramyl dipeptide (MDP), and the leucine-rich repeat motif was responsible for the recognition and binding of PaNOD2 with the ligand. Overexpression of PaNOD2 activated the NF-κB signaling pathway, leading to the upregulation of inflammatory cytokines, including TNF-α and IL-1β in HEK293T cells and ayu head kidney-derived monocytes/macrophages (MO/MΦ). Particularly, we found that PaNOD2 activated the MAPK signaling pathways, as indicated by the increased phosphorylation of p-38, Erk1/2, and JNK1/2, which have not been characterized in any teleost species previously. Our findings proved that the NOD2 molecule and initiated pathways are conserved between mammals and ayu. Therefore, ayu could be used as an animal model to investigate NOD2-based diseases and therapeutic applications.

     

/

返回文章
返回