前期研究发现,信号淋巴细胞活化分子(signaling lymphocyte activation molecule,SLAM or CD150)和脊髓灰质炎病毒受体相关蛋白4(poliovirus receptor-related protein 4,PVRL4 or Nectin4)是麻疹病毒属副黏病毒的主要细胞受体,也参与...前期研究发现,信号淋巴细胞活化分子(signaling lymphocyte activation molecule,SLAM or CD150)和脊髓灰质炎病毒受体相关蛋白4(poliovirus receptor-related protein 4,PVRL4 or Nectin4)是麻疹病毒属副黏病毒的主要细胞受体,也参与禽副黏病毒NDV感染的感染过程[1]。为了验证鸡源Nectin4(chNectin4)和鸡源SLAM(chSLAM)在NDV感染中的作用,本研究构建了分别稳定表达chNectin4和chSLAM的BHK21细胞系。感染实验结果显示,稳定表达chNectin4和chSLAM细胞系在接种NDV La Sota株后12 h和24 h NP mRNA水平显著高于亲本细胞,表明chNectin4和chSLAM有助于促进NDV在BHK21细胞系中的增殖,其中chNectin4的促NDV增殖作用更加明显。本研究为进一步研究鸡Nectin4和SLAM在NDV感染中的作用以及NDV疫苗的研究奠定了基础。展开更多
Early-life stress(ES)leads to cognitive dysfunction in female adolescents,but the underlying neural mechanisms remain elusive.Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role i...Early-life stress(ES)leads to cognitive dysfunction in female adolescents,but the underlying neural mechanisms remain elusive.Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role in cognition and ES-related cognitive deficits in male rodents.In this study,we aimed to investigate whether and how nectins contribute to ES-induced cognitive dysfunction in female adolescents.Applying the well-established limited bedding and nesting material paradigm,we found that ES impairs recognition memory,suppresses prefrontal NECTIN1 and hippocampal NECTIN3 expression,and upregulates corticotropin-releasing hormone(Crh)and its receptor 1(Crhr1)mRNA levels in the hippocampus of adolescent female mice.Genetic experiments revealed that the reduction of dorsal CA1(dCA1)NECTIN3 mediates ES-induced object recognition memory deficits,as knocking down dCA1 NECTIN3 impaired animals’performance in the novel object recognition task,while overexpression of dCA1 NECTIN3 successfully reversed the ES-induced deficits.Notably,prefrontal NECTIN1 knockdown did not result in significant cognitive impairments.Furthermore,acute systemic administration of antalarmin,a CRHR1 antagonist,upregulated hippocampal NECTIN3 levels and rescued object and spatial memory deficits in stressed mice.Our findings underscore the critical role of dCA1 NECTIN3 in mediating ES-induced object recognition memory deficits in adolescent female mice,highlighting it as a potential therapeutic target for stress-related psychiatric disorders in women.展开更多
目的探讨Nectin-4在卵巢癌细胞株SKOV3中的表达及其在体外侵袭和转移中的作用。方法构建Nectin-4真核表达载体,以脂质体介导转染卵巢癌细胞SKOV3,用RT-PCR和免疫组织化学法检测SKOV3 Nectin-4mRNA及蛋白表达水平。结果转染Nectin-4的实...目的探讨Nectin-4在卵巢癌细胞株SKOV3中的表达及其在体外侵袭和转移中的作用。方法构建Nectin-4真核表达载体,以脂质体介导转染卵巢癌细胞SKOV3,用RT-PCR和免疫组织化学法检测SKOV3 Nectin-4mRNA及蛋白表达水平。结果转染Nectin-4的实验组细胞与转染空载体的对照组细胞比较,Nectin-4 mRNA的表达量差异有统计学意义(0.84±0.09 vs 0.37±0.05,P<0.01);Nectin-4蛋白表达水平差异有统计学意义(0.67±0.10 vs 0.16±0.09,P<0.01)。Boyden小室体外侵袭实验中实验组与对照组平均侵袭百分数分别为(46.0±6.07)%、(25.3±7.56)%,差异有统计学意义(P<0.05)。结论Nectin-4增强了卵巢癌细胞SKOV3体外侵袭和转移的能力,其机制与Nectin-4增强细胞的运动能力及增殖能力有关。展开更多
文摘前期研究发现,信号淋巴细胞活化分子(signaling lymphocyte activation molecule,SLAM or CD150)和脊髓灰质炎病毒受体相关蛋白4(poliovirus receptor-related protein 4,PVRL4 or Nectin4)是麻疹病毒属副黏病毒的主要细胞受体,也参与禽副黏病毒NDV感染的感染过程[1]。为了验证鸡源Nectin4(chNectin4)和鸡源SLAM(chSLAM)在NDV感染中的作用,本研究构建了分别稳定表达chNectin4和chSLAM的BHK21细胞系。感染实验结果显示,稳定表达chNectin4和chSLAM细胞系在接种NDV La Sota株后12 h和24 h NP mRNA水平显著高于亲本细胞,表明chNectin4和chSLAM有助于促进NDV在BHK21细胞系中的增殖,其中chNectin4的促NDV增殖作用更加明显。本研究为进一步研究鸡Nectin4和SLAM在NDV感染中的作用以及NDV疫苗的研究奠定了基础。
基金supported by the National Natural Science Foundation of China(82271569,82001418,82371530,82171529,and 82071528)the Beijing Natural Science Foundation(7222236)the Capital Medical Development Research Fund(2022-1-4111)。
文摘Early-life stress(ES)leads to cognitive dysfunction in female adolescents,but the underlying neural mechanisms remain elusive.Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role in cognition and ES-related cognitive deficits in male rodents.In this study,we aimed to investigate whether and how nectins contribute to ES-induced cognitive dysfunction in female adolescents.Applying the well-established limited bedding and nesting material paradigm,we found that ES impairs recognition memory,suppresses prefrontal NECTIN1 and hippocampal NECTIN3 expression,and upregulates corticotropin-releasing hormone(Crh)and its receptor 1(Crhr1)mRNA levels in the hippocampus of adolescent female mice.Genetic experiments revealed that the reduction of dorsal CA1(dCA1)NECTIN3 mediates ES-induced object recognition memory deficits,as knocking down dCA1 NECTIN3 impaired animals’performance in the novel object recognition task,while overexpression of dCA1 NECTIN3 successfully reversed the ES-induced deficits.Notably,prefrontal NECTIN1 knockdown did not result in significant cognitive impairments.Furthermore,acute systemic administration of antalarmin,a CRHR1 antagonist,upregulated hippocampal NECTIN3 levels and rescued object and spatial memory deficits in stressed mice.Our findings underscore the critical role of dCA1 NECTIN3 in mediating ES-induced object recognition memory deficits in adolescent female mice,highlighting it as a potential therapeutic target for stress-related psychiatric disorders in women.
文摘目的探讨Nectin-4在卵巢癌细胞株SKOV3中的表达及其在体外侵袭和转移中的作用。方法构建Nectin-4真核表达载体,以脂质体介导转染卵巢癌细胞SKOV3,用RT-PCR和免疫组织化学法检测SKOV3 Nectin-4mRNA及蛋白表达水平。结果转染Nectin-4的实验组细胞与转染空载体的对照组细胞比较,Nectin-4 mRNA的表达量差异有统计学意义(0.84±0.09 vs 0.37±0.05,P<0.01);Nectin-4蛋白表达水平差异有统计学意义(0.67±0.10 vs 0.16±0.09,P<0.01)。Boyden小室体外侵袭实验中实验组与对照组平均侵袭百分数分别为(46.0±6.07)%、(25.3±7.56)%,差异有统计学意义(P<0.05)。结论Nectin-4增强了卵巢癌细胞SKOV3体外侵袭和转移的能力,其机制与Nectin-4增强细胞的运动能力及增殖能力有关。
