鸡 miR-148a-3p 通过靶向 MAPK 信号通路和 IFN-γ 调节针对 AIV 的免疫反应,Veterinary Research

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鸡 miR-148a-3p 通过靶向 MAPK 信号通路和 IFN-γ 调节针对 AIV 的免疫反应
Veterinary Research ( IF 3.7 ) Pub Date : 2023-11-22 , DOI: 10.1186/s13567-023-01240-3
Thi Hao Vu _{1,

2} , Yeojin Hong ₁ , Jubi Heo ₁ , Suyeon Kang ₁ , Hyun S Lillehoj ₃ , Yeong Ho Hong ₁

Affiliation

MicroRNA 参与宿主动物的免疫系统，并在多种免疫相关途径中发挥重要作用。在当前的研究中，我们研究了鸡 miRNA gga-miR-148a-3p 对 HPAIV-H5N1 耐药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的表达显着下调。gga-miR-148a 和带有野生型或突变型 IFN-γ、MAPK11 和 TGF-β2 3' 非翻译区 (3' UTR)-荧光素酶的报告构建体在鸡成纤维细胞中的过表达表明，gga-miR-148a 充当通过靶向 IFN-γ、MAPK11 和 TGF-β2 的 3' UTR 来直接抑制其翻译。此外，miR-148a直接负面影响与MAPK信号通路相关的信号分子的表达，包括MAPK11、TGF-β2和Jun，并通过靶向干扰素刺激基因以及MHC I类和II类基因调节抗病毒反应。干扰素-γ。在 MAPK 信号通路下游，gga-miR-148a 的过表达会下调多种促炎细胞因子，如 IL-1β、IFN-γ、IL-6、TNF-α、IFN-β 和干扰素刺激基因。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、鸡对HPAIV-H5N1感染的抗病毒反应以及gga-miR-148a-3p的作用的理解提高鸡免疫反应的整体性能，以培育抗病鸡。

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Chicken miR-148a-3p regulates immune responses against AIV by targeting the MAPK signalling pathway and IFN-γ

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.

更新日期：2023-11-22

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