Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China; Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources (Shanghai Ocean University), Ministry of Education, China; National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, China.
Dev Comp Immunol. 2021 Apr;117:103976. doi: 10.1016/j.dci.2020.103976. Epub 2020 Dec 24.
The inflammatory response is a self-defense process that fights the pathogen invasion by eliminating harmful stimuli. However, excessive inflammation may disrupt immune homeostasis, even causing chronic inflammation or autoimmune diseases. MicroRNAs (miRNAs) are a crucial regulator that can negatively regulate gene expression and participate in multiple biological processes of growth, development, and immune response in organisms. However, the miRNA-mediated modulation networks of inflammatory responses remain largely unclear in lower vertebrates. In this study, miR-128 was identified as a negative regulator to participate in the NF-κB signaling pathway by targeting TAB2 in miiuy croaker. First, we predicted target genes of miR-128 through the bioinformatics software programs and found that TAB2 is a direct target of miR-128. We also found that miR-128 can inhibit TAB2 expression at the mRNA and protein levels. Besides, upon LPS stimulation, miR-128 inhibits the expression of inflammatory cytokines by targeting TAB2 to avoid excessive inflammation. Particularly, we found that miR-128 can regulate TAB2-mediated NF-κB signaling pathways. In summary, our results indicate that miR-128 plays a critical role in suppressing inflammatory responses by regulating the TAB2-mediated NF-κB signaling pathway in miiuy croaker.
炎症反应是一种自我防御过程,通过消除有害刺激来对抗病原体入侵。然而,过度的炎症反应可能会破坏免疫稳态,甚至导致慢性炎症或自身免疫性疾病。microRNAs(miRNAs)是一种重要的调节因子,可以负调控基因表达,并参与生物体生长、发育和免疫反应的多个生物学过程。然而,miRNAs 介导的炎症反应调节网络在低等脊椎动物中仍然很大程度上不清楚。在这项研究中,miR-128 被鉴定为通过靶向 miiuy 大黄鱼中的 TAB2 参与 NF-κB 信号通路的负调节剂。首先,我们通过生物信息学软件程序预测了 miR-128 的靶基因,发现 TAB2 是 miR-128 的直接靶标。我们还发现 miR-128 可以在 mRNA 和蛋白质水平上抑制 TAB2 的表达。此外,在 LPS 刺激下,miR-128 通过靶向 TAB2 抑制炎症细胞因子的表达,从而避免过度炎症。特别是,我们发现 miR-128 可以调节 TAB2 介导的 NF-κB 信号通路。总之,我们的研究结果表明,miR-128 通过调节 TAB2 介导的 NF-κB 信号通路在 miiuy 大黄鱼中发挥关键作用,抑制炎症反应。