Bacterial induced miR-144-5p modulates intestinal inflammatory response of Japanese flounder by targeting Hsp90α-dependent NLR signaling pathway
Bacterial induced miR-144-5p modulates intestinal inflammatory response of Japanese flounder by targeting Hsp90α-dependent NLR signaling pathway
复制标题
细菌诱导的miR - 144 - 5p通过靶向热休克蛋白90α（Hsp90α）依赖的NLR信号通路调节牙鲆肠道炎症反应
DOI：
10.1016/j.aquaculture.2022.739053
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发表时间：
2022-11
期刊：
影响因子：
4.5
通讯作者：
Yingrui Li;Lin Su;Baoshan Guo;Shun Zhou;Chao Li;Yunji Xiu
中科院分区：
文献类型：
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作者：
Yingrui Li;Lin Su;Baoshan Guo;Shun Zhou;Chao Li;Yunji Xiu
病原菌感染可诱导肠道炎症过程，适当的肠道炎症反应对鱼类有益，而过度的炎症反应改变了肠道内分泌信号，导致免疫反应失调。近年来，许多研究发现，硬骨鱼类microRNA在机体抗病原感染的天然免疫反应中起着重要的调节作用。然而，目前关于miRNAs介导的硬骨鱼类肠道炎症反应调控网络的研究较少。在我们的研究中，miR-144- 5 p被鉴定为硬骨鱼抗细菌感染的负调节因子。首先，在迟缓爱德华氏菌和脂多糖（LPS）刺激下，比目鱼体内和体外miR-144- 5 p的表达均显著上调，而Hsp 90 α、NLRP 3、Caspase 1和IL-1β的表达均显著下调。进一步证实miR-144- 5 p通过靶向Hsp 90 α依赖的NLR信号通路调控比目鱼肠道炎症反应，构建了miR-144- 5 p-Hsp 90 α-NLRP 3信号通路。此外，miR-144- 5 p-Hsp 90 α-NLRP 3信号通路可抑制比目鱼的抗菌免疫应答，促进大肠杆菌的存活。迟到。此外，该研究还表明miR-144- 5 p-Hsp 90 α调控网络在其他硬骨鱼和人类中广泛存在。结论：大肠杆菌攻击后，miR-144- 5 p的表达显著上调。LPS通过Hsp 90 α下调炎症相关细胞因子NLRP 3、Caspase 1和IL-1β的表达，最终促进细菌感染。本研究构建了一条新的miR-144- 5 p-Hsp 90 α-NLRP 3信号通路，丰富了miRNA对鱼类肠道黏膜免疫的调控网络，为鱼类疾病治疗策略的开发奠定了基础。
Pathogens infection could induce intestinal inflammatory processes, appropriate intestinal inflammation response had beneficial effects in fish, while excessive inflammation alters enteroendocrine signaling, leading to deregulated immune response. Recently, many researches revealed that microRNAs in teleost serve as vital regulators in innate immunity responses against pathogen infection. However, there are few studies on miRNAs mediated regulatory networks of intestinal inflammatory response in teleost. In our study, miR-144-5p was identified as negative regulators in teleost against bacterial infection. First, we found that the expression of miR-144-5p in flounder bothin vivoandin vitrowas significantly up-regulated, while the expression of Hsp90α, NLRP3, Caspase1 and IL-1β were significantly down-regulated upon the stimulation of Edwardsiella tarda and lipopolysaccharide (LPS). Furthermore, we confirmed that miR-144-5p modulates intestinal inflammatory responses of flounder by targeting Hsp90α-dependent NLR signaling pathway, in which the miR-144-5p-Hsp90α-NLRP3 signaling pathway was constructed. Besides, the miR-144-5p-Hsp90α-NLRP3 signaling pathway could inhibit antibacterial immune response of flounder and promote the survival ofE. tarda. Moreover, the study demonstrated that the miR-144-5p-Hsp90α regulatory network was widely existed in other teleost and human. In conclusion, the expression of miR-144-5p was significantly up-regulated after challenged byE. tardaand LPS, which then down-regulated the expression of inflammation-related cytokines of NLRP3, Caspase1 and IL-1β by targeting Hsp90α, and ultimately promoted bacterial infection. Our findings constructed a novel miR-144-5p-Hsp90α-NLRP3 signaling pathway, which enriched the regulatory network of miRNA on fish intestinal mucosal immunity and would benefit the development of fish disease therapeutic strategies to prevent potentially lethal bacterial infection.