流感病毒WSN毒株通过TGF-β1/Smad3介导的STAT3磷酸化调控类黏蛋白的表达  

Influenza A/WSN/33 virus regulates the expression of orosomucoid through STAT3 phosphorylation mediated by TGF-β1/Smad3

作　　者：尤冬雪 潘宸 陈玉章 周欣霓 高铭 陈梦颖 王佳俊 池晓娟[1,2,3] 王松 YOU Dongxue;PAN Chen;CHEN Yuzhang;ZHOU Xinni;GAO Ming;CHEN Mengying;WANG Jiajun;CHI Xiaojuan;WANG Song(College of Animal Sciences,Fujian Agriculture and Forestry University,Fuzhou,Fujian,China;Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province,Fuzhou,Fujian,China;Key Laboratory of Fujian-Taiwan Animal Pathogen Biology,Fuzhou,Fujian,China)

机构地区：[1]福建农林大学动物科学学院,福建福州 [2]福建省畜禽病原感染与免疫学重点实验室,福建福州 [3]闽台动物病原生物学福建省高校重点实验室,福建福州

出　　处：《微生物学报》2025年第2期771-780,共10页Acta Microbiologica Sinica

基　　金：福建省自然科学基金(2020J06016);福建农林大学科技创新专项基金(KFb22063XA)。

摘　　要：【目的】探究TGF-β1/Smad3在流感病毒WSN毒株感染过程中对类黏蛋白(orosomucoid,ORM)表达的调控作用。【方法】利用流感病毒WSN毒株感染或TGF-β1处理A549细胞,然后使用Smad3抑制剂处理,通过RT-PCR检测ORM的表达情况;构建过表达STAT3的细胞系与敲低STAT3的细胞系,通过RT-PCR和Western blotting方法检测STAT3在流感病毒诱导ORM表达中的作用;使用TGF-β1处理A549细胞,通过Western blotting方法检测p-STAT3表达情况;使用TGF-β1或流感病毒处理A549细胞,然后使用Smad3抑制剂处理,检测p-STAT3表达情况;构建Smad3表达敲低细胞系,通过Western blotting方法检测STAT3磷酸化水平。【结果】TGF-β1调控ORM1和ORM2的表达依赖于Smad3的活化;STAT3在流感病毒感染过程中参与了ORM1和ORM2的表达调控;TGF-β1能够诱导STAT3发生磷酸化;阻断Smad3的活化或敲低Smad3表达后,TGF-β1或WSN诱导的STAT3的磷酸化也被抑制。【结论】流感病毒WSN毒株调控ORM1和ORM2的表达依赖于TGF-β1/Smad3介导的STAT3磷酸化。[Objective]To investigate the regulatory effect of transforming growth factor-beta 1(TGF-β1)/Smad3 on orosomucoid(ORM)expression during infection with influenza A/WSN/33virus(hereinafter referred to as WSN).[Methods]A549 cells were either infected with WSN or treated with TGF-β1,followed by treatment with Smad3 inhibitors.The mRNA levels of ORMs were assessed by RT-PCR.Subsequently,cell lines with signal transducer and activator of transcription 3(STAT3)overexpression and knockdown were established,and RT-PCR and Western blotting were employed to evaluate the impact of STAT3 on ORM expression induced by the influenza virus.Furthermore,A549 cells underwent treatment with TGF-β1,after which the phosphorylation status of STAT3 was analyzed via Western blotting.Finally,the phosphorylation level of STAT3 was detected after inhibiting the activity of Smad3 or knocking down the expression of Smad3 in A549 cells infected with WSN or treated with TGF-β1.[Results]TGF-β1regulated the expression of ORM1 and ORM2 through the activation of Smad3,a key mediator in the TGF-βsignaling pathway.Concurrently,STAT3 was implicated in modulating ORM1 and ORM2 expression during WSN infection.Additionally,TGF-β1 was shown to induce STAT3phosphorylation.Notably,inhibiting Smad3 activation or knocking down Smad3 expression suppressed STAT3 phosphorylation.[Conclusion]The regulation of ORM1 and ORM2 expression by WSN relied on STAT3 phosphorylation mediated by TGF-β1/Smad3.

关 键 词：流感病毒 TGF-β1/Smad3 STAT3 类黏蛋白 

分 类 号：S852.65[农业科学—基础兽医学]