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生长激素(GH)通过激活PI3K/Akt信号通路抑制禽白血病病毒-J(ALV-J)复制并限制细胞周期。

GH inhibits ALV-J replication and restricts cell cycle by activating PI3K/Akt signaling pathway.

作者信息

Xia Junliang, Lin Ling, Ju Rongyang, Xu Chengxun, Mo Guodong, Zhang Xiquan

机构信息

Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, PR China; Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, Guangzhou, Guangdong, PR China; State Key Laboratory of Swine and Poultry Breeding Industry, Guangzhou, PR China.

Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, PR China; Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, Guangzhou, Guangdong, PR China; State Key Laboratory of Swine and Poultry Breeding Industry, Guangzhou, PR China; Guangxi Vocational University of Agriculture, Nanning, 530007 Guangxi, PR China.

出版信息

Poult Sci. 2025 Jan;104(1):104514. doi: 10.1016/j.psj.2024.104514. Epub 2024 Nov 13.

DOI:10.1016/j.psj.2024.104514
PMID:39586129
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11625326/
Abstract

Growth hormone (GH) plays a crucial role in growth, sexual maturity, and immunity in chickens. Avian leukosis virus subgroup J (ALV-J) is an exogenous tumorigenic retrovirus that primarily induces immunosuppression, growth retardation, decreased egg production, tumors formation, and even death in chickens. Previous studies have suggested that GH is involved in the regulation of innate immunity and inflammation. However, the specific role of GH in response to ALV-J remains unclear. In this study, we observed a significant upregulation of GH protein expression in the plasma of ALV infected chickens, and a marked increase in GH mRNA in ALV-J infected cells. We found that lower gp85 expression correlated with higher GH expression in immune tissues, suggesting that GH may inhibit gp85 expression. Additionally, GH overexpression enhanced the expression of interferons (IFN-α, IFN-β), interferon-stimulating genes (Mx1, ASCL1, CH25H), and pro-inflammatory factors (Mx1, ASCL1, CH25H) in DF-1 cells infected with ALV-J. GH also affected the cell cycle by regulating the expression of cell proliferation-related genes (p21, PCNA, Cyclin B2, Cyclin D1, Cyclin D2) and cell apoptosis-related genes (p53, Fas, Cyct, Caspase-1, Caspase-3, Caspase-8). More importantly, we found that GH restricted cell proliferation and apoptosis, and inhibited the replication of ALV-J by activating the PI3K/Akt signaling pathway in DF-1 cells. In conclusion, these results indicate GH plays a role in the antiviral response against the replication of ALV-J, providing evidence of an interaction between GH and the innate immunity in chickens.

摘要

生长激素(GH)在鸡的生长、性成熟和免疫中起着至关重要的作用。禽白血病病毒J亚群(ALV-J)是一种外源性致瘤逆转录病毒,主要诱导鸡的免疫抑制、生长迟缓、产蛋量下降、肿瘤形成甚至死亡。先前的研究表明,GH参与先天免疫和炎症的调节。然而,GH在应对ALV-J时的具体作用仍不清楚。在本研究中,我们观察到ALV感染鸡血浆中GH蛋白表达显著上调,且ALV-J感染细胞中GH mRNA明显增加。我们发现免疫组织中较低的gp85表达与较高的GH表达相关,这表明GH可能抑制gp85表达。此外,GH过表达增强了感染ALV-J的DF-1细胞中干扰素(IFN-α、IFN-β)、干扰素刺激基因(Mx1、ASCL1、CH25H)和促炎因子(Mx1、ASCL1、CH25H)的表达。GH还通过调节细胞增殖相关基因(p21、PCNA、细胞周期蛋白B2、细胞周期蛋白D1、细胞周期蛋白D2)和细胞凋亡相关基因(p53、Fas、Cyct、半胱天冬酶-1、半胱天冬酶-3、半胱天冬酶-8)的表达来影响细胞周期。更重要的是,我们发现GH通过激活DF-1细胞中的PI3K/Akt信号通路来限制细胞增殖和凋亡,并抑制ALV-J的复制。总之,这些结果表明GH在针对ALV-J复制的抗病毒反应中发挥作用,为鸡体内GH与先天免疫之间的相互作用提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce6/11625326/0cd6120d2911/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce6/11625326/6ab05e08d8d5/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce6/11625326/5a116ebc23a4/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce6/11625326/15837237f288/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce6/11625326/a86b90263ac7/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce6/11625326/05d60d150b36/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce6/11625326/0cd6120d2911/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce6/11625326/6ab05e08d8d5/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce6/11625326/5a116ebc23a4/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce6/11625326/15837237f288/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce6/11625326/a86b90263ac7/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce6/11625326/05d60d150b36/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce6/11625326/0cd6120d2911/gr6.jpg

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