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The role of methyltransferase-like 3 (METTL3) in immune response modulation in bivalve (Mytilus coruscus) during bacterial infection 甲基转移酶样3 (METTL3)在双壳贝(Mytilus coruscus)细菌感染期间免疫反应调节中的作用
IF 4.1 2区 农林科学 Q1 FISHERIES Pub Date : 2025-02-01 DOI: 10.1016/j.fsi.2024.110094
Xirui Si, Xinglu Chen, Baoying Guo, Zhi Liao, Xiaojun Yan, Pengzhi Qi
N6-methyladenosine (m6A) modification is a prevalent mRNA modification that regulates diverse biological processes in eukaryotes, including immune responses. While the role of m6A in mammalian immunity has been explored, its involvement in the immune defense of invertebrates, particularly marine bivalves which face constant pathogen challenges, remains largely unknown. Here, we investigated the function of methyltransferase-like 3 (METTL3), a key m6A "writer" enzyme, in the immune response of the marine bivalve Mytilus coruscus against Vibrio alginolyticus infection. M. coruscus METTL3 (McMETTL3) expression in the digestive gland increased (3-fold) after V. alginolyticus infection, coinciding with elevated m6A levels. Silencing McMETTL3 reduced both m6A levels and V. alginolyticus-induced apoptosis in digestive gland cells. In silico analysis identified a C1q-like protein family member (McC1QL) as a potential downstream target of McMETTL3, exhibiting an increase (7.2-fold) in m6A modification and an increase (1.5-fold) in expression during infection. Functional experiments confirmed that McC1QL knockdown inhibited McMETTL3-driven apoptosis (10.83 %). These findings demonstrate that METTL3 regulates apoptosis and immune responses in invertebrates via m6A modification of target genes like McC1QL. This study provides novel insights into the m6A-mediated immune regulation mechanisms in marine bivalves and may offer potential avenues for developing innovative disease control strategies in aquaculture.
n6 -甲基腺苷(m6A)修饰是一种普遍的mRNA修饰,可调节真核生物的多种生物过程,包括免疫反应。虽然已经探索了m6A在哺乳动物免疫中的作用,但它在无脊椎动物,特别是面临持续病原体挑战的海洋双壳类动物的免疫防御中的作用仍然很大程度上未知。本文研究了甲基转移酶样3 (methyltransferase-like 3, METTL3)在海洋双壳贝贻贝(Mytilus coruscus)抗溶藻弧菌(Vibrio alginolyticus)感染的免疫应答中的作用。McMETTL3 (McMETTL3)在溶藻弧菌感染后消化腺中的表达增加(3倍),与m6A水平升高相一致。沉默McMETTL3可降低m6A水平和溶藻毒杆菌诱导的消化腺细胞凋亡。在计算机分析中发现了一个c1q样蛋白家族成员(McC1QL)作为McMETTL3的潜在下游靶点,在感染期间m6A修饰增加(7.2倍),表达增加(1.5倍)。功能实验证实,mc1ql敲低抑制mcmettl3驱动的细胞凋亡(10.83%)。这些发现表明,METTL3通过m6A修饰靶基因如McC1QL来调节无脊椎动物的细胞凋亡和免疫应答。该研究为海洋双壳类动物m6a介导的免疫调节机制提供了新的见解,并可能为开发创新的水产养殖疾病控制策略提供潜在的途径。
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引用次数: 0
m6A methylation dynamically participates in the immune response against Vibrio anguillarum in half-smooth tongue sole (Cynoglossus semilaevis) m6A甲基化动态参与半光滑舌底(Cynoglossus semiaevis)对鳗弧菌的免疫应答。
IF 4.1 2区 农林科学 Q1 FISHERIES Pub Date : 2025-02-01 DOI: 10.1016/j.fsi.2024.110101
Suxu Tan , Wenwen Wang , Sen Han , Ruixue Zhang , Kunpeng Shi , Shaoqing Zang , Zhendong Wu , Zhenxia Sha
N6-methyladenosine (m6A) is the most prevalent RNA modification and a multifaceted regulator capable of affecting various aspects of mRNA metabolism, thereby playing important roles in numerous physiological processes. However, it is still unknown whether, when, and to what extent m6A modulation are implicated in the immune response of an economically important aquaculture fish, half-smooth tongue sole (Cynoglossus semilaevis). Herein, we systematically profiled and characterized the m6A epitranscriptome and transcriptome in C. semilaevis after the infection of Vibrio anguillarum. We demonstrated that m6A could be modulated as early as 4-h post infection (hpi), and the overall intensity of m6A methylation was enhanced following infection. Both conservative and novel motifs were uncovered from the m6A modification sites. Furthermore, differentially m6A methylated genes (DMGs) and differentially expressed genes (DEGs) were identified, and functional enrichment revealed multiple immune-related pathways, especially the FoxO signaling pathway which showed significance in every comparison. Joint analysis highlighted the remarkedly dynamic role of m6A on gene expression, i.e. early on, m6A mainly prioritized the down-regulation of specific genes, and later, it switched gears to promote expression of another set of genes. Moreover, key candidate genes, mainly involved in immunity and energy metabolism, were identified. Validations were performed by qPCR and MeRIP-qPCR. To our limited knowledge, this is the first study comprehensively characterizing the global m6A atlas in aquaculture fish species. The presented results provide new insights into the dynamics of m6A modifications in the transcriptome of the half-smooth tongue sole following bacterial infection, and further studies are warranted to elucidate the functional significance of these changes in depth.
n6 -甲基腺苷(n6 - methylladenosine, m6A)是一种最常见的RNA修饰物,也是一种多方面的调节剂,能够影响mRNA代谢的各个方面,从而在许多生理过程中发挥重要作用。然而,目前尚不清楚m6A调节是否、何时以及在多大程度上与一种经济上重要的水产养殖鱼类半光滑舌鳎(Cynoglossus semiaevis)的免疫反应有关。在此,我们系统地分析和表征了C. semiaevis感染鳗弧菌后的m6A表转录组和转录组。我们证明m6A可以在感染后4小时(hpi)被调节,并且感染后m6A甲基化的总体强度增强。从m6A修饰位点发现了保守的和新的基序。此外,还鉴定了m6A差异甲基化基因(dmg)和差异表达基因(DEGs),功能富集揭示了多种免疫相关途径,特别是FoxO信号通路,在各比较中均显示出显著性。联合分析发现,m6A对基因表达的影响是再显著的动态作用,即m6A在早期主要优先下调特定基因的表达,后来又转而促进另一组基因的表达。此外,还确定了主要参与免疫和能量代谢的关键候选基因。采用qPCR和MeRIP-qPCR进行验证。据我们所知,这是第一个全面表征全球水产养殖鱼类m6A图谱的研究。本研究结果为细菌感染后半光滑舌底转录组中m6A修饰的动态变化提供了新的见解,需要进一步的研究来深入阐明这些变化的功能意义。
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引用次数: 0
SENP2 negatively regulates RIG-I/MDA5 mediated innate immunity in black carp SENP2负调控黑鱼rig - 1 /MDA5介导的先天免疫。
IF 4.1 2区 农林科学 Q1 FISHERIES Pub Date : 2025-02-01 DOI: 10.1016/j.fsi.2024.110097
Yixia Chen , Jun Li , Jiaxin Fu , Lili Xiao , Jixiang Chu , Wei Qin , Jun Xiao , Hao Feng
Mammalian SUMO specific peptidase 2 (SENP2) plays vital roles in a variety of biological procedures including the immune response. However, the effects of teleost SENP2 are still mostly unexplored. In this study, the SENP2 of black carp (Mylopharyngodon piceus) was cloned and characterized. The open reading frame of black carp SENP2 (bcSENP2) consists of 1800 nucleotides, which encode 600 amino acids. The reporter assay results showed that over-expression of bcSENP2 alone had a weak effect on interferon (IFN) promoter transcription activity, whereas it significantly reduced bcMDA5/bcRIG-I mediated IFN promoter transcription activity. The interaction between bcSENP2 and bcMDA5 or bcRIG-I was detected by immunoprecipitation experiments. The plaque assay and qPCR results indicated that bcMDA5 or bcRIG-I mediated antiviral capacity was attenuated by bcSENP2, while knockdown of bcSENP2 led to enhanced antiviral resistance to SVCV in host cells. In addition, the expression level of bcMDA5/bcRIG-I protein was attenuated by co-expressed bcSENP2 and MG132 treatment rescued this attenuating effect. All of these data support the conclusion that bcSENP2 inhibits bcMDA5/bcRIG-I mediated antiviral signaling by enhancing ubiquitin-proteasome mediated degradation of bcMDA5/bcRIG-I in black carp.
哺乳动物SUMO特异性肽酶2 (SENP2)在包括免疫反应在内的多种生物过程中发挥重要作用。然而,硬骨鱼SENP2的作用大部分仍未被探索。本研究对青鱼(Mylopharyngodon piceus)的SENP2基因进行了克隆和鉴定。黑鱼SENP2 (bcSENP2)开放阅读框由1800个核苷酸组成,编码600个氨基酸。报告基因实验结果显示,单独过表达bcSENP2对干扰素(IFN)启动子转录活性的影响较弱,而过表达bcMDA5/ bcrig - 1介导的IFN启动子转录活性显著降低。通过免疫沉淀实验检测bcSENP2与bcMDA5或bcrig - 1的相互作用。斑块分析和qPCR结果表明,bcSENP2可减弱bcMDA5或bcrig - 1介导的抗病毒能力,而bcSENP2的敲低可增强宿主细胞对SVCV的抗病毒抗性。此外,通过共表达bcSENP2, bcMDA5/ bcrig - 1蛋白的表达水平被减弱,MG132处理恢复了这种减弱作用。这些数据支持bcSENP2通过增强泛素蛋白酶体介导的bcMDA5/ bcrig - 1降解来抑制黑鱼bcMDA5/ bcrig - 1介导的抗病毒信号通路的结论。
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引用次数: 0
MALT1 promotes the antibacterial immune response by activating NF-κB signaling and enhancing hemocyte phagocytosis in the Chinese mitten crab MALT1通过激活NF-κB信号,增强中华绒螯蟹血细胞吞噬能力,促进抗菌免疫应答。
IF 4.1 2区 农林科学 Q1 FISHERIES Pub Date : 2025-02-01 DOI: 10.1016/j.fsi.2024.110100
Guoqing Shen , Guangyu Wang , Jinming Chen , Yanan Guo , Wen Zhang , Chaohui Xu , Liqiao Chen , Qun Wang
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), a scaffold protein, plays a pivotal role in the NF-κB pathway downstream of T-cell receptors (TCRs) and B-cell receptors (BCRs). As a key signaling hub, MALT1 integrates various pathways, making it essential for both innate and adaptive immunity. However, its role in the antibacterial immune responses of crustaceans remains unclear. Here, we characterized MALT1 from the Chinese mitten crab (Eriocheir sinensis), denoted as EsMALT1, and compared its sequence and domain conservation with MALT1 from other species. Furthermore, Vibrio parahaemolyticus infection upregulated EsMALT1 expression markedly. Knockdown of EsMALT1 in hemocytes inhibits the translocation of the NF-κB-like transcription factors EsRelish and EsDorsal from the cytoplasm to the nucleus in response to Vibrio parahaemolyticus stimulation, thereby reducing the expression of the antimicrobial peptides anti-lipopolysaccharide factor (ALF), and Crustins. At the cellular level, silencing of EsMALT1 expression significantly inhibited the phagocytic capacity of crab hemocytes against Vibrio parahaemolyticus. In vivo, silencing of EsMALT1 rendered crabs susceptible to bacterial infection and impaired their bacterial clearance. In conclusion, EsMALT1 promotes both humoral and cellular immunity in E. sinensis, making it essential for the induction of antibacterial immune responses.
粘膜相关淋巴组织淋巴瘤易位蛋白1 (MALT1)是一种支架蛋白,在t细胞受体(TCRs)和b细胞受体(BCRs)下游的NF-κB通路中起关键作用。作为一个关键的信号中枢,MALT1整合了多种途径,使其对先天免疫和适应性免疫都至关重要。然而,其在甲壳类动物的抗菌免疫反应中的作用尚不清楚。本文对中华绒螯蟹(Eriocheir sinensis)的MALT1进行了鉴定,记为EsMALT1,并将其序列和结构域保守性与其他物种的MALT1进行了比较。此外,副溶血性弧菌感染显著上调了EsMALT1的表达。血细胞中敲低EsMALT1可抑制NF-κ b样转录因子esspit和EsDorsal在副溶血性弧菌刺激下从细胞质向细胞核的易位,从而降低抗菌肽抗脂多糖因子(anti- lipopolyaccharide factor, ALF)和甲壳蛋白的表达。在细胞水平上,沉默EsMALT1表达可显著抑制螃蟹血细胞对副溶血性弧菌的吞噬能力。在体内,沉默EsMALT1使螃蟹易受细菌感染,并削弱其细菌清除能力。综上所述,EsMALT1可促进中华赤霉素的体液免疫和细胞免疫,对诱导抗菌免疫应答至关重要。
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引用次数: 0
FADD cooperates with Caspase-8 to positively regulate the innate immune response and promote apoptosis following bacterial infection in Japanese eel FADD与Caspase-8协同正向调节日本鳗鲡细菌感染后的先天免疫反应,促进细胞凋亡。
IF 4.1 2区 农林科学 Q1 FISHERIES Pub Date : 2025-02-01 DOI: 10.1016/j.fsi.2024.110110
Tianyu Wang , Peng Lin , Yilei Wang , Yun Chen , Ziping Zhang , Fuyan Li , Jianjun Feng
Fas-associated protein with Death Domain (FADD) is a crucial signaling component of apoptosis and a vital immunomodulator on inflammatory signaling pathways. However, information on FADD-mediated apoptosis and immune regulation is limited in teleost. We herein cloned a FADD homolog, AjFADD, from Japanese eel (Anguilla japonica). Expression analysis revealed that AjFADD was significantly induced by LPS, poly I:C, and Aeromonas hydrophila infection in vivo and in vitro. The expression of IFNs and IRFs, c-Rel and c-Fos, IL1 and TNF-α, and the essential antimicrobial peptide LEAP-2 in Japanese eel liver cells was enhanced by overexpressing AjFADD, with a significant decrease of those genes following knockdown AjFADD. Luciferase activity assay, flow cytometry, and wound healing results showed that AjFADD cooperated with AjCaspase-8 to promote apoptosis of HEK293 cells and Japanese eel liver cells infected with A. hydrophila. Furthermore, AjFADD and AjCaspase-8 co-localized in the cytoplasm and displayed a direct protein-protein interaction by immunoprecipitation. Our results collectively showed that FADD cooperated with Caspase-8 to positively regulate the innate immune response and promote apoptosis in response to the A. hydrophila challenge in Japanese eel.
fas相关蛋白与死亡结构域(FADD)是细胞凋亡的重要信号成分,也是炎症信号通路的重要免疫调节剂。然而,关于fadd介导的硬骨鱼细胞凋亡和免疫调节的信息有限。本文从日本鳗鲡(Anguilla japonica)中克隆了一个FADD同源基因AjFADD。表达分析表明,体内外AjFADD均受LPS、poly I:C和嗜水气单胞菌感染的显著诱导。过表达AjFADD后,日本鳗鲡肝细胞中p65、c-Rel、c-Jun、c-Fos、IL1、IL6和必需抗菌肽LEAP-2的表达增强,而敲低AjFADD后,这些基因的表达显著降低。荧光素酶活性测定、流式细胞术及伤口愈合结果显示,AjFADD与AjCaspase-8协同作用可促进HEK293细胞及嗜水单胞菌感染的日本鳗鲡肝细胞凋亡。此外,AjFADD和AjCaspase-8在细胞质中共定位,并通过免疫沉淀表现出直接的蛋白相互作用。综上所述,FADD与Caspase-8共同作用,正向调节日本鳗鲡对嗜水拟南鳗的先天免疫反应,促进细胞凋亡。
{"title":"FADD cooperates with Caspase-8 to positively regulate the innate immune response and promote apoptosis following bacterial infection in Japanese eel","authors":"Tianyu Wang ,&nbsp;Peng Lin ,&nbsp;Yilei Wang ,&nbsp;Yun Chen ,&nbsp;Ziping Zhang ,&nbsp;Fuyan Li ,&nbsp;Jianjun Feng","doi":"10.1016/j.fsi.2024.110110","DOIUrl":"10.1016/j.fsi.2024.110110","url":null,"abstract":"<div><div>Fas-associated protein with Death Domain (FADD) is a crucial signaling component of apoptosis and a vital immunomodulator on inflammatory signaling pathways. However, information on FADD-mediated apoptosis and immune regulation is limited in teleost. We herein cloned a FADD homolog, <em>Aj</em>FADD, from Japanese eel (<em>Anguilla japonica</em>). Expression analysis revealed that <em>Aj</em>FADD was significantly induced by LPS, poly I:C, and <em>Aeromonas hydrophila</em> infection <em>in vivo</em> and <em>in vitro</em>. The expression of <em>IFNs</em> and <em>IRFs</em>, <em>c-Rel</em> and <em>c-Fos</em>, <em>IL1</em> and <em>TNF-α</em>, and the essential antimicrobial peptide <em>LEAP-2</em> in Japanese eel liver cells was enhanced by overexpressing <em>Aj</em><em>FADD</em>, with a significant decrease of those genes following knockdown <em>Aj</em><em>FADD</em>. Luciferase activity assay, flow cytometry, and wound healing results showed that <em>Aj</em>FADD cooperated with <em>Aj</em>Caspase-8 to promote apoptosis of HEK293 cells and Japanese eel liver cells infected with <em>A. hydrophila</em>. Furthermore, <em>Aj</em>FADD and <em>Aj</em>Caspase-8 co-localized in the cytoplasm and displayed a direct protein-protein interaction by immunoprecipitation. Our results collectively showed that FADD cooperated with Caspase-8 to positively regulate the innate immune response and promote apoptosis in response to the <em>A. hydrophila</em> challenge in Japanese eel.</div></div>","PeriodicalId":12127,"journal":{"name":"Fish & shellfish immunology","volume":"157 ","pages":"Article 110110"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Seaweed residue hydrolysate enhances the intestinal health, immunity and disease resistance in northern snakehead (Channa argus) 海藻渣水解物对北方黑鱼肠道健康、免疫力和抗病性有促进作用。
IF 4.1 2区 农林科学 Q1 FISHERIES Pub Date : 2025-02-01 DOI: 10.1016/j.fsi.2025.110115
Minmin Wang , Wenwen Wang , Lei Guo , Suxu Tan , Hongtao Xue , Ya Wang , Xiao Cao , Mengyang Chang , Kunpeng Shi , Yanzhao Nie , Yingming Yang , Zhenxia Sha
Seaweed residue hydrolysate (SRH), produced by the acid hydrolysis of seaweed processing residues, is rich in bioactive compounds. The development and utilization of SRH as an aquatic immune enhancer not only achieves high-value utilization of waste but also promotes green and healthy aquaculture. In this study, northern snakehead (Channa argus) juveniles fed a compound feed supplemented with SRH (treatment group) exhibited a significant enhancement in intestinal microbial diversity and the proliferation of beneficial bacteria after eight weeks. After Edwardsiella tarda infection, the survival of the treatment group (70 %) was significantly higher than that in the control group (30 %). Histological analysis revealed that SRH alleviated tissue damage incurred by bacterial infection. Compared to the control group, the treatment group demonstrated an increase in the activities of non-specific immune enzymes and antioxidant enzymes, as well as a decrease in malondialdehyde (MDA). Furthermore, SRH influenced intestinal gene expression, with differentially expressed genes (DEGs) being enriched in various immune-related pathways, including cAMP, intestinal immune network for IgA production, and NF-κB signaling pathways. The present study has elucidated the potential efficacy of SRH in mitigating oxidative stress, enhancing the immunity and disease resistance of northern snakehead, providing valuable insights into the high-value utilization of SRH as a sustainable and eco-friendly immune enhancer in aquaculture.
海藻渣水解物(SRH)是由海藻加工残渣酸水解而产生的富含生物活性物质。SRH作为水生免疫增强剂的开发利用,既实现了废弃物的高价值利用,又促进了绿色健康养殖。在本研究中,饲喂添加SRH的配合饲料(处理组)8周后,北方黑鱼幼鱼肠道微生物多样性和有益菌增殖显著增强。延迟爱德华菌感染后,治疗组的生存率(70%)显著高于对照组(30%)。组织学分析显示,SRH可减轻细菌感染引起的组织损伤。与对照组相比,治疗组表现出非特异性免疫酶和抗氧化酶活性的增加,以及丙二醛(MDA)的降低。此外,SRH影响肠道基因表达,差异表达基因(DEGs)在多种免疫相关通路中富集,包括cAMP、肠道免疫网络产生IgA和NF-κB信号通路。本研究阐明了SRH在缓解北方蛇头氧化应激、增强免疫力和抗病性方面的潜在功效,为SRH作为可持续生态免疫增强剂在水产养殖中的高价值利用提供了有价值的见解。
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引用次数: 0
Molecular characterization, transcriptional profiling, and antioxidant activity assessment of nucleoredoxin (NXN) as a novel member of thioredoxin from red-lip mullet (Planiliza haematocheilus) 红唇鲻鱼(Planiliza haematocheilus)硫氧还蛋白新成员核氧还蛋白(NXN)的分子特征、转录分析和抗氧化活性评估。
IF 4.1 2区 农林科学 Q1 FISHERIES Pub Date : 2025-02-01 DOI: 10.1016/j.fsi.2024.110104
M.A.H. Dilshan , W.K.M. Omeka , H.M.V. Udayantha , D.S. Liyanage , D.C.G. Rodrigo , G.A.N.P. Ganepola , W.A.D.L.R. Warnakula , H.A.C.R. Hanchapola , Y.K. Kodagoda , Jeongeun Kim , Gaeun Kim , Jihun Lee , Qiang Wan , Jehee Lee
Nucleoredoxin (NXN) is a prominent oxidoreductase enzyme, classified under the thioredoxin family, and plays a pivotal role in regulating cellular redox homeostasis. Although the functional characterization of NXN has been extensively studied in mammals, its role in fish remains relatively unexplored. In this study, the NXN gene from Planiliza haematocheilus (PhNXN) was molecularly and functionally characterized using in silico tools, expression analyses, and in vitro assays. The predicted protein sequence of PhNXN contained 418 amino acids with an anticipated molecular mass of 47.53 kDa. It comprised a highly conserved 188CPPC191 catalytic motif in the central NXN domain and two thioredoxin-like domains enriched with conserved Cys residues. PhNXN protein was primarily localized in the cytoplasm and nucleus of the cells. The spatial and temporal expression analyses of PhNXN mRNA showed the highest expression level in the brain under normal physiological conditions, while a significant modulation was detected in the blood and head kidney following immunostimulation with polyinosinic: polycytidylic acid, lipopolysaccharides, and Lactococcus garvieae. Recombinant PhNXN protein exhibited DPPH radical scavenging, thiol-dependent disulfide reduction, and cupric ion reduction activities. Additionally, PhNXN overexpression significantly suppressed oxidative stress-induced cell death, heavy metal cation-induced reactive oxygen species production, and viral hemorrhagic septicemia virus-induced cellular apoptosis in fish cells. Furthermore, PhNXN overexpression in RAW 264.7 cells demonstrated notable nitric oxide scavenging activity, M2-type polarization, and anti-inflammatory effect. Collectively, the overall findings of the study highlight the antioxidant and immunological functions of PhNXN in red-lip mullet.
核氧还蛋白(NXN)是一种重要的氧化还原酶,属于硫氧还蛋白家族,在调节细胞氧化还原稳态中起关键作用。虽然NXN的功能特征已经在哺乳动物中得到了广泛的研究,但它在鱼类中的作用仍然相对未知。在这项研究中,利用硅工具、表达分析和体外实验对haematocheilus Planiliza NXN基因(PhNXN)进行了分子和功能表征。预测的PhNXN蛋白序列包含418个氨基酸,预计分子质量为47.53 kDa。它由一个高度保守的位于中心NXN结构域的188CPPC191催化基序和两个富含保守Cys残基的硫氧还蛋白样结构域组成。PhNXN蛋白主要定位于细胞质和细胞核中。PhNXN mRNA的时空表达分析显示,正常生理条件下,PhNXN mRNA在大脑中的表达水平最高,而在多肌苷、多胞酸、脂多糖和garvieae乳球菌免疫刺激后,在血液和头肾中表达显著调节。重组PhNXN蛋白具有清除DPPH自由基、巯基依赖性二硫还原和铜离子还原活性。此外,PhNXN过表达显著抑制氧化应激诱导的细胞死亡、重金属阳离子诱导的活性氧产生和病毒性出血性败血症病毒诱导的细胞凋亡。此外,PhNXN在RAW 264.7细胞中过表达表现出显著的一氧化氮清除活性、m2型极化和抗炎作用。总之,本研究的总体发现突出了PhNXN在红唇鲻鱼中的抗氧化和免疫功能。
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引用次数: 0
SIGIRR plays a dual role in zebrafish infected with Edwardsiella piscicida: Boosting digestive system wellness and mitigating inflammation SIGIRR在斑马鱼感染爱德华氏菌中起双重作用:促进消化系统健康和减轻炎症。
IF 4.1 2区 农林科学 Q1 FISHERIES Pub Date : 2025-02-01 DOI: 10.1016/j.fsi.2024.110105
Ting Yu , Shuo Yang , Lifeng Zhang , Dan Deng , Xiao Zhang , Kai Luo , Weihua Gao , Bei Wang , Shuhuan Zhang , Qiaoqing Xu
Single immunoglobulin interleukin-1 receptor-associated protein (SIGIRR) negatively regulates the inflammatory response induced by bacterial infection by inhibiting the excessive synthesis of inflammatory mediators and overactivation. This inhibitory mechanism reduces the fish's susceptibility to pathogens and enhances survival rates. Zebrafish lacking the SIGIRR gene were generated using CRISPR/Cas9 gene knockout technology. In a zebrafish model infected with Edwardsiella piscicida, researchers found that SIGIRR gene deletion led to a significant increase in the activation of both inflammatory and anti-inflammatory factors. This deletion also resulted in intestinal villus epithelium damage, epithelial shedding, separation of the epithelium and lamina propria, and a severe reduction in goblet cells. After E. piscicida infection, the survival rate of SIGIRR−/− zebrafish was significantly reduced, and the number of E. piscicida in the body was also significantly increased. Intestinal acid phosphatase activity in SIGIRR−/− zebrafish was markedly elevated compared to wild-type (WT) zebrafish. Furthermore, the intestinal mucosal layer and villus thickness in SIGIRR−/− zebrafish were reduced compared to WT zebrafish. The enzymatic activities of lipase and lysozyme in the intestines of SIGIRR−/− zebrafish were significantly lower than in WT zebrafish. This study reveals the detrimental effects of SIGIRR gene deletion on the intestinal health of zebrafish, leading to decreased innate immune capacity and increased susceptibility to bacterial infections.
单免疫球蛋白白介素-1受体相关蛋白(SIGIRR)通过抑制炎症介质的过度合成和过度激活,负向调节细菌感染诱导的炎症反应。这种抑制机制降低了鱼对病原体的易感性,提高了存活率。利用CRISPR/Cas9基因敲除技术产生SIGIRR基因缺失的斑马鱼。在感染了淡化鱼爱德华菌的斑马鱼模型中,研究人员发现SIGIRR基因缺失导致炎症和抗炎因子的激活显著增加。这种缺失还导致肠绒毛上皮损伤,上皮脱落,上皮和固有层分离,杯状细胞严重减少。SIGIRR-/-斑马鱼感染后,SIGIRR-/-斑马鱼的存活率显著降低,体内的淡化鱼数量也显著增加。SIGIRR-/-斑马鱼肠道酸性磷酸酶活性与野生型(WT)斑马鱼相比显著升高。此外,与WT斑马鱼相比,SIGIRR-/-斑马鱼的肠粘膜层和绒毛厚度减少。SIGIRR-/-斑马鱼肠道脂肪酶和溶菌酶活性显著低于WT斑马鱼。本研究揭示了SIGIRR基因缺失对斑马鱼肠道健康的不利影响,导致先天免疫能力下降,对细菌感染的易感性增加。
{"title":"SIGIRR plays a dual role in zebrafish infected with Edwardsiella piscicida: Boosting digestive system wellness and mitigating inflammation","authors":"Ting Yu ,&nbsp;Shuo Yang ,&nbsp;Lifeng Zhang ,&nbsp;Dan Deng ,&nbsp;Xiao Zhang ,&nbsp;Kai Luo ,&nbsp;Weihua Gao ,&nbsp;Bei Wang ,&nbsp;Shuhuan Zhang ,&nbsp;Qiaoqing Xu","doi":"10.1016/j.fsi.2024.110105","DOIUrl":"10.1016/j.fsi.2024.110105","url":null,"abstract":"<div><div>Single immunoglobulin interleukin-1 receptor-associated protein (SIGIRR) negatively regulates the inflammatory response induced by bacterial infection by inhibiting the excessive synthesis of inflammatory mediators and overactivation. This inhibitory mechanism reduces the fish's susceptibility to pathogens and enhances survival rates. Zebrafish lacking the SIGIRR gene were generated using CRISPR/Cas9 gene knockout technology. In a zebrafish model infected with <em>Edwardsiella piscicida</em>, researchers found that SIGIRR gene deletion led to a significant increase in the activation of both inflammatory and anti-inflammatory factors. This deletion also resulted in intestinal villus epithelium damage, epithelial shedding, separation of the epithelium and lamina propria, and a severe reduction in goblet cells. After <em>E. piscicida</em> infection, the survival rate of SIGIRR<sup>−/−</sup> zebrafish was significantly reduced, and the number of <em>E. piscicida</em> in the body was also significantly increased. Intestinal acid phosphatase activity in SIGIRR<sup>−/−</sup> zebrafish was markedly elevated compared to wild-type (WT) zebrafish. Furthermore, the intestinal mucosal layer and villus thickness in SIGIRR<sup>−/−</sup> zebrafish were reduced compared to WT zebrafish. The enzymatic activities of lipase and lysozyme in the intestines of SIGIRR<sup>−/−</sup> zebrafish were significantly lower than in WT zebrafish. This study reveals the detrimental effects of SIGIRR gene deletion on the intestinal health of zebrafish, leading to decreased innate immune capacity and increased susceptibility to bacterial infections.</div></div>","PeriodicalId":12127,"journal":{"name":"Fish & shellfish immunology","volume":"157 ","pages":"Article 110105"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Astragaloside IV can mitigate heat stress-induced tissue damage through modulation of the Keap1-Nrf2 signaling pathway in grass carp (Ctenopharyngodon idella) 黄芪甲苷可通过调节草鱼Keap1-Nrf2信号通路减轻热应激诱导的草鱼组织损伤。
IF 4.1 2区 农林科学 Q1 FISHERIES Pub Date : 2025-02-01 DOI: 10.1016/j.fsi.2025.110121
Hua Liu , Jingjing Feng , Xiaoxue Bao , Qi Wang , Haiyi Yu , Hui Yu , Ying Yang
This study investigated the potential protective effect of AS-IV against heat stress-induced tissue damage in grass carp (Ctenopharyngodon idella). Grass carp were injected intraperitoneally with 0, 2, 4, and 8 mg/kg of AS-IV for three consecutive days, and then subjected to heat stress (35 ± 0.5 °C); thereafter, histopathological analyses of the liver and spleen were performed at 0, 6, 24, and 48 h, respectively. The results indicated that sustained heat stress resulted in hemorrhage, vacuolization, increased hepatic blood sinusoidal space, inflammatory cell infiltration in the liver, and decreased number of melanomacrophage centers in the spleen; conversely, 4 and 8 mg/kg AS-IV attenuated the pathological symptoms induced by heat stress and mitigated tissue damage in the liver and spleen of grass carp. The possible mechanism is that AS-IV promotes Nrf2 signaling through the downregulation of keap1a and keap1b, thereby activating the Keap1–Nrf2 signaling pathway, leading to changes in the levels of protection-related genes in the liver (GSH-Px and CAT levels were elevated while MDA levels were decreased, and gsh-px, cat, cu-zn sod, and hsp70 mRNA levels were upregulated while il-6 mRNA levels were downregulated) and spleen (GSH-Px, CAT, SOD, and GSH levels were increased while MDA levels were decreased, and il-6 mRNA levels were downregulated), which, in turn, improves the antioxidant ability of grass carp. Additionally, an appropriate dose of AS-IV transiently increased complement C3 levels after sustained heat stress, thereby improving the immunity of grass carp under heat stress. In conclusion, AS-IV can mitigate tissue damage induced in response to heat stress by modulating the redox homeostasis of grass carp and can be practically implemented in aquaculture sector.
本研究探讨了AS-IV对草鱼热应激诱导的组织损伤的潜在保护作用。草鱼连续3天腹腔注射0、2、4和8 mg/kg AS-IV,然后进行热应激(35±0.5℃);之后,分别于0、6、24和48 h对肝脏和脾脏进行组织病理学分析。结果表明,持续热应激导致大鼠出血、空泡化、肝血窦间隙增大、肝脏炎症细胞浸润、脾脏巨噬细胞中心数量减少;相反,4和8 mg/kg AS-IV可减轻草鱼热应激引起的病理症状,减轻肝、脾组织损伤。可能的机制是AS-IV通过下调keap1a和keap1b来促进Nrf2信号通路,从而激活Keap1-Nrf2信号通路,导致肝脏(GSH-Px和CAT水平升高而MDA水平降低,GSH-Px、CAT、cu-zn sod和hsp70 mRNA水平上调而il-6 mRNA水平下调)和脾脏(GSH-Px、CAT、sod、提高和GSH水平,降低MDA水平,下调il-6 mRNA水平),从而提高草鱼的抗氧化能力。此外,适当剂量的AS-IV可在持续热应激后短暂增加补体C3水平,从而提高草鱼在热应激下的免疫力。综上所述,AS-IV可通过调节草鱼氧化还原稳态来减轻热应激对草鱼组织的损伤,可在养殖业中实际应用。
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引用次数: 0
ARRDC3, a novel α-arrestin, modulates WSSV replication and AHPND pathogenesis in Litopeneaus vannamei ARRDC3是一种新型α-抑制蛋白,可调节凡纳滨对虾WSSV的复制和AHPND的发病机制。
IF 4.1 2区 农林科学 Q1 FISHERIES Pub Date : 2025-02-01 DOI: 10.1016/j.fsi.2024.110074
Ramya Kumar , Brandon Rafael de Jesús Castillo-Corea , Shih-Shun Lin , Chien-Kang Huang , Han-Ching Wang
Although shrimp are a valuable protein source, shrimp aquaculture has numerous challenges from various infectious diseases and understanding molecular mechanisms of disease pathogenesis is crucial for disease management. In this study, a gene-to-gene correlation network generated from a transcriptomic database of the stomach of shrimp infected with acute hepatopancreatic necrosis disease (AHPND) was used to identify a new α-arrestin, termed arrestin domain containing-3 gene (LvARRDC3), with crucial roles in development of both AHPND and white spot disease (WSD). Double stranded RNA-mediated silencing or plasmid-mediated overexpression of LvARRDC3 gene significantly decreased expression of WSSV genes (IE1, VP28, and ICP11) and viral genome copy numbers. Nevertheless, in AHPND, silencing the LvARRDC3 gene increased the AHPND-associated plasmid and Pir toxins copy numbers, whereas overexpression of LvARRDC3 had the opposite effect. An in vitro pathogen binding assay with recombinant LvARRDC3 protein produced robust binding to WSSV virions and AHPND-causing V. parahaemolyticus. Moreover, based on immunofluorescence, LvARRDC3 was localized in the cytoplasm of Spodoptera frugiperda (Sf9) insect cells. Therefore, we inferred that LvARRDC3 has a role in pathogen internalization, making it a valuable target for addressing AHPND and WSD and also a biomarker for marker-associated shrimp breeding.
尽管对虾是一种宝贵的蛋白质来源,但对虾养殖面临着各种传染病的挑战,了解疾病发病的分子机制对疾病管理至关重要。本研究利用侵染急性肝胰腺坏死病(AHPND)的虾胃转录组学数据库建立基因-基因相关网络,鉴定出一种新的α-抑制蛋白,称为抑制蛋白结构域-3基因(LvARRDC3),该基因在AHPND和白斑病(WSD)的发展中都起着至关重要的作用。双链rna介导的LvARRDC3基因沉默或质粒介导的LvARRDC3基因过表达显著降低WSSV基因(IE1、VP28和ICP11)的表达和病毒基因组拷贝数。然而,在AHPND中,沉默LvARRDC3基因会增加AHPND相关质粒和Pir毒素的拷贝数,而过表达LvARRDC3则会产生相反的效果。重组LvARRDC3蛋白与WSSV病毒粒子和引起ahpnd的副溶血性弧菌进行了体外病原体结合试验。此外,基于免疫荧光,LvARRDC3定位于Spodoptera frugiperda (Sf9)昆虫细胞的细胞质中。因此,我们推断LvARRDC3在病原体内化中发挥作用,使其成为解决AHPND和WSD的有价值的靶点,也是标记相关对虾育种的生物标志物。
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引用次数: 0
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Fish & shellfish immunology
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