Zhou Linxin, Li Jiayi, Sun Xinxin, Xin Yingying, Yin Shaowu, Ning Xianhui
Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Jiangsu Key Laboratory of Ocean-Land Environmental Change and Ecological Construction, School of Marine Science and Engineering, Nanjing Normal University, Nanjing 210023, Jiangsu, China.
Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Jiangsu Key Laboratory of Ocean-Land Environmental Change and Ecological Construction, School of Marine Science and Engineering, Nanjing Normal University, Nanjing 210023, Jiangsu, China; Co-Innovation Center for Marine Bio-Industry Technology of Jiangsu Province, Lianyungang 222005, China.
Comp Biochem Physiol C Toxicol Pharmacol. 2025 Mar;289:110121. doi: 10.1016/j.cbpc.2025.110121. Epub 2025 Jan 7.
The intricate interaction among host, pathogen, and environment significantly influences aquatic health, yet the influence of hypoxic stress combined with bacterial infection on host response is understudied. Circular RNAs with stable closed-loop structures have emerged as important regulators in immunity, yet remain ill-defined in fish. In this study, we systematically explored the circRNA response in yellow catfish subjected to combined hypoxia-bacterial infection (HB) stress. Following HB stress, H&E and TUNEL staining identified heightened hepatocyte apoptosis, intracellular vacuolation, and inflammatory tissue damage. RT-qPCR elucidated that differentially expressed genes stimulated by HB synergistically enhanced apoptosis and inflammatory responses. Importantly, we systematically evaluated differentially expressed circRNAs (DEcirs) in yellow catfish under hypoxia with and without Aeromonas veronii infection and identified a novel HB-specific DEcir, designated as circArid4b, whose parental gene Arid4b is highly associated with apoptosis. Experiments confirmed the circular structure of circArid4b and revealed that under HB stimulation, specific knockdown of circArid4b inhibited the expression of Arid4b, while concurrent alterations in multiple apoptosis- and inflammation-related genes synergistically indicated the promotion of apoptotic and inflammatory pathways. Notably, the downregulation of circArid4b expression significantly reduced the susceptibility to bacterial infection in yellow catfish during hypoxia. These results suggest that HB-induced suppression of circArid4b promotes cell apoptosis and inflammation by inhibiting its parental gene and thereby facilitating resistance to bacterial infection during hypoxia. Our study enriches the understanding of fish circRNA mechanisms and offers novel preventive and control strategies for bacterial infections in fish under hypoxic environments.
宿主、病原体和环境之间复杂的相互作用显著影响水生生物健康，但低氧应激与细菌感染相结合对宿主反应的影响仍未得到充分研究。具有稳定闭环结构的环状RNA已成为免疫过程中的重要调节因子，但在鱼类中仍未明确。在本研究中，我们系统地探索了杂交鲇在低氧-细菌联合感染（HB）应激下的环状RNA反应。在HB应激后，苏木精-伊红染色和TUNEL染色显示肝细胞凋亡增加、细胞内空泡化以及炎症性组织损伤。逆转录定量聚合酶链反应表明，由HB刺激的差异表达基因协同增强了凋亡和炎症反应。重要的是，我们系统评估了在有或没有维氏气单胞菌感染的低氧条件下杂交鲇的差异表达环状RNA（DEcirs），并鉴定出一种新的HB特异性DEcir，命名为circArid4b，其亲本基因Arid4b与凋亡高度相关。实验证实了circArid4b的环状结构，并表明在HB刺激下，特异性敲低circArid4b会抑制Arid4b的表达，而多个凋亡和炎症相关基因的同时改变协同表明凋亡和炎症途径得到促进。值得注意的是，circArid4b表达的下调显著降低了杂交鲇在低氧期间对细菌感染的易感性。这些结果表明，HB诱导的circArid4b抑制通过抑制其亲本基因促进细胞凋亡和炎症，从而在低氧期间促进对细菌感染的抗性。我们的研究丰富了对鱼类环状RNA机制的理解，并为低氧环境下鱼类细菌感染提供了新的预防和控制策略。
