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SHP-1 interacts with NFκB1 to inhibit its phosphorylation and nuclear translocation to exert its anti-bacterial function

文献类型： 外文期刊

作者： Wang, Ningning 1 ; Tan, Suxu 1 ; Wang, Muyuan 1 ; Liu, Hongning 1 ; Han, Sen 1 ; Wu, Zhendong 1 ; Ma, Jie 1 ; Chen, Songlin 1 ; Sha, Zhenxia 1 ;

作者机构： 1.Qingdao Univ, Inst Aquat Biotechnol, Coll Life Sci, Qingdao 266071, Peoples R China

2.Qingdao Univ, Coll Basic Med, Qingdao 266071, Peoples R China

3.Chinese Acad Fishery Sci, Yellow Sea Fisheries Res Inst, State Key Lab Mariculture Biobreeding & Sustainabl, Qingdao 266071, Shandong, Peoples R China

4.Qingdao Marine Sci & Technol Ctr, Lab Marine Fisheries Sci & Food Prod Proc, Qingdao 266237, Shandong, Peoples R China

关键词： SHP-1; Immune response; Phosphorylation of NF kappa B1; Nuclear translocation

期刊名称：AQUACULTURE （ 影响因子：3.9； 五年影响因子：4.4 ）

ISSN： 0044-8486

年卷期： 2025 年 599 卷

页码：

收录情况： SCI

摘要： The protein tyrosine phosphatase SHP-1 plays pivotal roles in maintaining cellular homeostasis, proliferation, and differentiation. Although SHP-1 has been shown to have anti-inflammatory effects in mammals, its potential anti-bacterial effects and regulatory mechanisms have not been elucidated in teleost. Chinese tongue sole (Cynoglossus semilaevis), an economically important aquaculture flatfish, has been widely used as a genomics and disease model. Herein, using this fish species, we demonstrated the function of SHP-1 in vitro and in vivo and further revealed the underlying mechanism in immune response caused by Vibrio anguillarum. Overexpression of SHP-1 decreased mortality and alleviated histopathological deterioration of Chinese tongue sole, while its inhibition exhibited the opposite effects. Accordingly, SHP-1 inhibited the activation/transduction of the toll like receptor 5-myeloid differentiation primary response 88-nuclear factor kappa-B (TLR5-MYD88-NF kappa B) axis and the secretion of pro-inflammatory cytokines. Most importantly, we revealed for the first time that SHP-1 inhibits Nuclear Factor Kappa B Subunit 1 (NF kappa B1) phosphorylation and nuclear translocation by interacting with NF kappa B1, thereby suppressing the activation of NF kappa B signaling and blocking excessive inflammation caused by bacteria and lipopolysaccharide (LPS). In summary, our findings systematically dissect the functions of SHP-1 in bacterial inflammation using Chinese tongue sole, and provide mechanistic insights into the control of bacterial diseases in aquaculture.

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