Department of Animal Science and Technology, Chung-Ang University, Anseong, 17546, Republic of Korea.
Department of Biochemistry and Immunology, National Institute of Veterinary Research, Hanoi, 100000, Vietnam.
Vet Res. 2023 Nov 22;54(1):110. doi: 10.1186/s13567-023-01240-3.
MicroRNAs are involved in the immune systems of host animals and play essential roles in several immune-related pathways. In the current study, we investigated the systemic biological function of the chicken miRNA gga-miR-148a-3p on immune responses in chicken lines resistant and susceptible to HPAIV-H5N1. We found that gga-miR-148a expression in the lung tissue of H5N1-resistant chickens was significantly downregulated during HPAIV-H5N1 infection. Overexpression of gga-miR-148a and a reporter construct with wild type or mutant IFN-γ, MAPK11, and TGF-β2 3' untranslated region (3' UTR)-luciferase in chicken fibroblasts showed that gga-miR-148a acted as a direct translational repressor of IFN-γ, MAPK11, and TGF-β2 by targeting their 3' UTRs. Furthermore, miR-148a directly and negatively influenced the expression of signalling molecules related to the MAPK signalling pathway, including MAPK11, TGF-β2, and Jun, and regulated antiviral responses through interferon-stimulated genes and MHC class I and class II genes by targeting IFN-γ. Downstream of the MAPK signalling pathway, several proinflammatory cytokines such as IL-1β, IFN-γ, IL-6, TNF-α, IFN-β, and interferon-stimulated genes were downregulated by the overexpression of gga-miR-148a. Our data suggest that gga-miR-148a-3p is an important regulator of the MAPK signalling pathway and antiviral response. These findings improve our understanding of the biological functions of gga-miR-148a-3p, the mechanisms underlying the MAPK signalling pathway, and the antiviral response to HPAIV-H5N1 infection in chickens as well as the role of gga-miR-148a-3p in improving the overall performance of chicken immune responses for breeding disease-resistant chickens.
微小 RNA 参与宿主动物的免疫系统，并在几个免疫相关途径中发挥重要作用。在本研究中，我们研究了鸡 miRNA gga-miR-148a-3p 对 HPAIV-H5N1 抗性和易感鸡系免疫反应的系统生物学功能。我们发现，在 HPAIV-H5N1 感染期间，H5N1 抗性鸡的肺组织中 gga-miR-148a 的表达显著下调。gga-miR-148a 在鸡成纤维细胞中的过表达以及具有野生型或突变 IFN-γ、MAPK11 和 TGF-β2 3'非翻译区（3'UTR）-荧光素酶的报告构建体表明，gga-miR-148a 通过靶向它们的 3'UTR 作为 IFN-γ、MAPK11 和 TGF-β2 的直接翻译抑制剂。此外，miR-148a 通过靶向 IFN-γ直接负调控与 MAPK 信号通路相关的信号分子的表达，包括 MAPK11、TGF-β2 和 Jun，并通过干扰素刺激基因和 MHC Ⅰ类和Ⅱ类基因调节抗病毒反应。在 MAPK 信号通路的下游，通过过表达 gga-miR-148a，几种促炎细胞因子，如 IL-1β、IFN-γ、IL-6、TNF-α、IFN-β 和干扰素刺激基因的表达被下调。我们的数据表明，gga-miR-148a-3p 是 MAPK 信号通路和抗病毒反应的重要调节因子。这些发现提高了我们对 gga-miR-148a-3p 的生物学功能、MAPK 信号通路的机制以及鸡对 HPAIV-H5N1 感染的抗病毒反应的理解，以及 gga-miR-148a-3p 在改善鸡免疫反应整体性能以培育抗病鸡方面的作用。
