Zhu Songwei, Yue Xinyuan, Huang Kejing, Li Xionglin, Gouife Moussa, Nawaz Mateen, Ma Rongrong, Jiang Jianhu, Jin Shan, Xie Jiasong
School of Marine Sciences, Ningbo University, Ningbo, Zhejiang Province, 315211, China.
School of Marine Sciences, Ningbo University, Ningbo, Zhejiang Province, 315211, China; Key Laboratory of Aquacultural Biotechnology, Ministry of Education, Ningbo University, Ningbo, Zhejiang Province, 315211, China.
Fish Shellfish Immunol. 2023 Mar;134:108616. doi: 10.1016/j.fsi.2023.108616. Epub 2023 Feb 15.
Nigericin has been reported to induce apoptosis and pyroptosis in mammalian models. However, the effects and mechanism underlying the immune responses of teleost HKLs induced by nigericin remain enigmatic. To decipher the mechanism after nigericin treatment, the transcriptomic profile of goldfish HKLs was analyzed. The results demonstrated that a total of 465 differently expressed genes (DEGs) with 275 up-regulated and 190 down-regulated genes were identified between the control and nigericin treated groups. Among them, the top 20 DEG KEGG enrichment pathways were observed including apoptosis pathways. In addition, the expression level of selected genes (ADP4, ADP5, IRE1, MARCC, ALR1, DDX58) by quantitative real-time PCR showed a significant change after treatment with nigericin, which was generally identical to the expression patterns of the transcriptomic data. Furthermore, the treatment could induce cell death of HKLs, which was confirmed by LDH release and annexin V-FITC/PI assays. Taken together, our results support the idea that nigericin treatment might activate the IRE1-JNK apoptosis pathway in goldfish HKLs, which will provide insights into the mechanisms underlying HKLs immunity towards apoptosis or pyroptosis regulation in teleosts.
据报道，尼日利亚菌素可在哺乳动物模型中诱导细胞凋亡和焦亡。然而，尼日利亚菌素诱导硬骨鱼HKLs免疫反应的作用及潜在机制仍不清楚。为了解析尼日利亚菌素处理后的机制，分析了金鱼HKLs的转录组概况。结果表明，在对照组和尼日利亚菌素处理组之间共鉴定出465个差异表达基因（DEGs），其中275个基因上调，190个基因下调。其中，观察到前20个DEG KEGG富集途径，包括凋亡途径。此外，通过定量实时PCR检测选定基因（ADP4、ADP5、IRE1、MARCC、ALR1、DDX58）的表达水平，发现尼日利亚菌素处理后有显著变化，这与转录组数据的表达模式基本一致。此外，该处理可诱导HKLs细胞死亡，这通过乳酸脱氢酶释放和膜联蛋白V-FITC/PI检测得以证实。综上所述，我们的结果支持以下观点：尼日利亚菌素处理可能激活金鱼HKLs中的IRE1-JNK凋亡途径，这将为硬骨鱼HKLs对凋亡或焦亡调节的免疫机制提供见解。
