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坏死性肠炎感染鸡品系脾脏中差异表达的JAK-STAT信号通路基因及靶标微小RNA

Differentially expressed JAK-STAT signaling pathway genes and target microRNAs in the spleen of necrotic enteritis-afflicted chicken lines.

作者信息

Truong Anh Duc, Rengaraj Deivendran, Hong Yeojin, Hoang Cong Thanh, Hong Yeong Ho, Lillehoj Hyun S

机构信息

Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea.

Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea.

出版信息

Res Vet Sci. 2017 Dec;115:235-243. doi: 10.1016/j.rvsc.2017.05.018. Epub 2017 May 13.

DOI:10.1016/j.rvsc.2017.05.018
PMID:28525837
Abstract

The JAK signal transducer and STAT signaling pathway is an important regulator of cell proliferation, differentiation, survival, motility, apoptosis, immune response, and development. In this study, we used RNA-Sequencing, qRT-PCR, and bioinformatics tools to investigate the differential expression of JAK-STAT pathway genes, their interactions, and regulators in the spleen of two genetically disparate chicken lines (Marek's disease-resistant line 6.3 and MD-susceptible line 7.2) induced necrotic enteritis (NE) disease by co-infection with Eimeria maxima and Clostridium perfringens. Using RNA-Seq analysis, we identified a total of 116 JAK-STAT pathway genes that were differentially expressed in the spleen of these chickens. All of the identified genes were analyzed through clustering, mapping to the KEGG chicken JAK-STAT pathway, and the Pathway Studio program. Of the 116 JAK-STAT pathway genes, 20 were further verified by qRT-PCR. According to the RNA-Seq results, several key genes, including STAT1-6, JAK1-3, TYK2, AKT1, AKT3, SOCS1-5, PIAS1, PIAS2, PIAS4, SHP1, SHP2, and PIK3, showed marked differential expression in the two lines, relative to their respective controls. Moreover, the RNA-Seq results of many key genes were highly correlated with the qRT-PCR results. Finally, we predicted 63 mature miRNAs that variably target JAK-STAT pathway genes and are differentially expressed in the spleen of chickens of both lines. To the best of our knowledge, this study is the first to analyze most of the genes, interactions, and regulators of the JAK-STAT pathway in the innate immune response to NE disease in chickens.

摘要

JAK信号转导子和STAT信号通路是细胞增殖、分化、存活、运动、凋亡、免疫反应及发育的重要调节因子。在本研究中,我们利用RNA测序、qRT-PCR和生物信息学工具,研究了两个遗传背景不同的鸡品系(抗马立克氏病品系6.3和马立克氏病易感品系7.2)在经巨型艾美耳球虫和产气荚膜梭菌共同感染诱导坏死性肠炎(NE)疾病时,脾脏中JAK-STAT通路基因的差异表达、它们之间的相互作用及调控因子。通过RNA-Seq分析,我们共鉴定出116个在这些鸡脾脏中差异表达的JAK-STAT通路基因。所有鉴定出的基因都通过聚类分析、映射到KEGG鸡JAK-STAT通路以及Pathway Studio程序进行了分析。在这116个JAK-STAT通路基因中,有20个通过qRT-PCR进一步验证。根据RNA-Seq结果,包括STAT1-6、JAK1-3、TYK2、AKT1、AKT3、SOCS1-5、PIAS1、PIAS2、PIAS4、SHP1、SHP2和PIK3在内的几个关键基因,相对于各自的对照组,在两个品系中表现出显著的差异表达。此外,许多关键基因的RNA-Seq结果与qRT-PCR结果高度相关。最后,我们预测了63个成熟的miRNA,它们可变地靶向JAK-STAT通路基因,并且在两个品系鸡的脾脏中差异表达。据我们所知,本研究首次分析了鸡对NE疾病先天性免疫反应中JAK-STAT通路的大多数基因、相互作用及调控因子。

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