High-mobility group box （HMGB） proteins, a family of chromatin-associated nuclear proteins, play amazingly multifaceted roles in the immune system of mammals. Thus far, little is known about the nucleocytoplasmic di...High-mobility group box （HMGB） proteins, a family of chromatin-associated nuclear proteins, play amazingly multifaceted roles in the immune system of mammals. Thus far, little is known about the nucleocytoplasmic distribution of HMGBs in teleosts. The present study systematically investigated the dynamic localization of all six HMGB proteins in Ctenopharyngodon idella kidney （CIK） cells. Under basal conditions, all HMGBs exclusively localized to the nucleus. Grass carp reovirus （GCRV）, polyinosinic-polycytidylic （poly（I ： C）） potassium salt and lipopolysaccharide （LPS） challenge evoked the nuclear export of HMGBs to various degrees： GCRV challenge induced the highest nuclear export of CiHMGB2b, and poly（I ~ C） and LPS evoked the highest nucleocytoplasmic shuttling of CiHMGBlb. Overall, the nucleocytoplasmic shuttling of CiHMGB2a and CiHMGB3b was rarely induced by these challenges. Dynamic imaging uncovered that the nucleocytoplasmic GCRV-induced relocation of CiHMGB2b occurred in cells undergoing karyotheca rupture, apoptosis or proliferation. Western blot analyses were used to examine HMGB-EGFP fusion proteins in whole cell lysates, cytosol, nuclear fractions and culture medium. Further investigation demonstrated the nuclear retention of N-terminal HMG-boxes and the nucleocytoplasmic distribution of the C-terminal acidic tails. Comparative analyses of the dynamic relocation of full-length, truncated or chimeric HMGBs confirmed that the intramolecular interaction between HMG-boxes and C-tail domains mediated the nucleocytoplasmic translocation of HMGBs. These results not only provide an overall understanding of the subcellular localization of HMGBs, but also reveal the induction mechanism of the nucleocytoplasmic translocation of HMGBs by GCRV challenge, which lays a foundation for further studies on the interactions among pathogens, HMGBs and pattern recognition receptors in the innate immunity of teleosts.展开更多
目的:检测慢性心力衰竭(CHF)患者血清Ⅲ型前胶原氨基末端前肽(N-terminal peptide of typeⅢprocollagen,PⅢNP)、高迁移率族蛋白B1(high mobility group box-1,HMGB1)的表达水平,探讨二者与左室射血分数(LVEF)的相关性以及对CHF的诊断...目的:检测慢性心力衰竭(CHF)患者血清Ⅲ型前胶原氨基末端前肽(N-terminal peptide of typeⅢprocollagen,PⅢNP)、高迁移率族蛋白B1(high mobility group box-1,HMGB1)的表达水平,探讨二者与左室射血分数(LVEF)的相关性以及对CHF的诊断价值。方法:收集2021年12月至2022年11月期间于佳木斯大学附属第一医院心内科住院治疗的慢性心力衰竭患者90例为实验组,按照LVEF将其分为HFrEF组(n=33)、HFmrEF组(n=27)和HFpEF组(n=30)。此外选取排除心功能不全诊断的同期住院患者30例为对照组。对比各组患者血清中氨基末端脑钠肽前体(NT-proBNP)、PⅢNP、HMGB1水平的差异,分析PⅢNP、HMGB1水平与心功能指标的相关性,并借助ROC曲线评估NT-proBNP、HMGB1、PⅢNP单独以及联合应用对不同表型CHF患者的诊断价值。结果:HFrEF组PⅢNP、HMGB1及NT-proBNP水平均高于HFpEF组和对照组,差异有统计学意义(P<0.05)。PⅢNP与HMGB1呈正相关(P<0.05);PⅢNP、HMGB1均与NT-proBNP、LVEDD呈正相关,与LVEF呈明显负相关(P<0.05);HMGB1与LAD呈正相关(P<0.05),PⅢNP与LAD无明显相关性(P>0.05)。血清NT-proBNP、HMGB1、PⅢNP水平诊断HFrEF患者的AUC分别为0.867、0.871、0.779;诊断HFmrEF患者的AUC分别为0.840、0.804、0.760;诊断HFpEF患者的AUC分别为0.851、0.728、0.769。多生物标志物模型NT-proBNP+PⅢNP、NT-proBNP+HMGB1、NT-proBNP+PⅢNP+HMGB1诊断HFrEF患者的AUC分别为0.887、0.954、0.954;诊断HFmrEF患者的AUC分别为0.942、0.937、0.951;诊断HFpEF患者的AUC分别为0.904、0.910、0.914。结论:CHF患者血清PⅢNP、HMGB1明显升高,并且,CHF患者血清PⅢNP、HMGB1水平与心脏功能指标具有良好的相关性,说明PⅢNP、HMGB1可反映疾病的严重程度。PⅢNP、HMGB1对各表型CHF患者均具有诊断价值,并且,多生物标志物联合检测能提高对CHF患者诊断的敏感性。展开更多
文摘High-mobility group box （HMGB） proteins, a family of chromatin-associated nuclear proteins, play amazingly multifaceted roles in the immune system of mammals. Thus far, little is known about the nucleocytoplasmic distribution of HMGBs in teleosts. The present study systematically investigated the dynamic localization of all six HMGB proteins in Ctenopharyngodon idella kidney （CIK） cells. Under basal conditions, all HMGBs exclusively localized to the nucleus. Grass carp reovirus （GCRV）, polyinosinic-polycytidylic （poly（I ： C）） potassium salt and lipopolysaccharide （LPS） challenge evoked the nuclear export of HMGBs to various degrees： GCRV challenge induced the highest nuclear export of CiHMGB2b, and poly（I ~ C） and LPS evoked the highest nucleocytoplasmic shuttling of CiHMGBlb. Overall, the nucleocytoplasmic shuttling of CiHMGB2a and CiHMGB3b was rarely induced by these challenges. Dynamic imaging uncovered that the nucleocytoplasmic GCRV-induced relocation of CiHMGB2b occurred in cells undergoing karyotheca rupture, apoptosis or proliferation. Western blot analyses were used to examine HMGB-EGFP fusion proteins in whole cell lysates, cytosol, nuclear fractions and culture medium. Further investigation demonstrated the nuclear retention of N-terminal HMG-boxes and the nucleocytoplasmic distribution of the C-terminal acidic tails. Comparative analyses of the dynamic relocation of full-length, truncated or chimeric HMGBs confirmed that the intramolecular interaction between HMG-boxes and C-tail domains mediated the nucleocytoplasmic translocation of HMGBs. These results not only provide an overall understanding of the subcellular localization of HMGBs, but also reveal the induction mechanism of the nucleocytoplasmic translocation of HMGBs by GCRV challenge, which lays a foundation for further studies on the interactions among pathogens, HMGBs and pattern recognition receptors in the innate immunity of teleosts.
文摘目的:检测慢性心力衰竭(CHF)患者血清Ⅲ型前胶原氨基末端前肽(N-terminal peptide of typeⅢprocollagen,PⅢNP)、高迁移率族蛋白B1(high mobility group box-1,HMGB1)的表达水平,探讨二者与左室射血分数(LVEF)的相关性以及对CHF的诊断价值。方法:收集2021年12月至2022年11月期间于佳木斯大学附属第一医院心内科住院治疗的慢性心力衰竭患者90例为实验组,按照LVEF将其分为HFrEF组(n=33)、HFmrEF组(n=27)和HFpEF组(n=30)。此外选取排除心功能不全诊断的同期住院患者30例为对照组。对比各组患者血清中氨基末端脑钠肽前体(NT-proBNP)、PⅢNP、HMGB1水平的差异,分析PⅢNP、HMGB1水平与心功能指标的相关性,并借助ROC曲线评估NT-proBNP、HMGB1、PⅢNP单独以及联合应用对不同表型CHF患者的诊断价值。结果:HFrEF组PⅢNP、HMGB1及NT-proBNP水平均高于HFpEF组和对照组,差异有统计学意义(P<0.05)。PⅢNP与HMGB1呈正相关(P<0.05);PⅢNP、HMGB1均与NT-proBNP、LVEDD呈正相关,与LVEF呈明显负相关(P<0.05);HMGB1与LAD呈正相关(P<0.05),PⅢNP与LAD无明显相关性(P>0.05)。血清NT-proBNP、HMGB1、PⅢNP水平诊断HFrEF患者的AUC分别为0.867、0.871、0.779;诊断HFmrEF患者的AUC分别为0.840、0.804、0.760;诊断HFpEF患者的AUC分别为0.851、0.728、0.769。多生物标志物模型NT-proBNP+PⅢNP、NT-proBNP+HMGB1、NT-proBNP+PⅢNP+HMGB1诊断HFrEF患者的AUC分别为0.887、0.954、0.954;诊断HFmrEF患者的AUC分别为0.942、0.937、0.951;诊断HFpEF患者的AUC分别为0.904、0.910、0.914。结论:CHF患者血清PⅢNP、HMGB1明显升高,并且,CHF患者血清PⅢNP、HMGB1水平与心脏功能指标具有良好的相关性,说明PⅢNP、HMGB1可反映疾病的严重程度。PⅢNP、HMGB1对各表型CHF患者均具有诊断价值,并且,多生物标志物联合检测能提高对CHF患者诊断的敏感性。
