We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repet...We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.展开更多
本试验旨在研究SH2B衔接因子蛋白1(SH2B adaptor protein 1,SH2B1)基因在猪不同组织和生长发育各阶段背部脂肪中的表达情况,预测调控该基因的miR-276-3p对猪背部脂肪表达的影响。应用实时荧光定量PCR技术检测SH2B1基因在猪脂肪、下丘脑...本试验旨在研究SH2B衔接因子蛋白1(SH2B adaptor protein 1,SH2B1)基因在猪不同组织和生长发育各阶段背部脂肪中的表达情况,预测调控该基因的miR-276-3p对猪背部脂肪表达的影响。应用实时荧光定量PCR技术检测SH2B1基因在猪脂肪、下丘脑等6种组织,以及在30、60、90、120和180 d猪背部脂肪组织中的相对表达量。靶标预测SH2B1基因的调控miRNA,并通过实时荧光定量PCR检测miR-276-3p对该基因的调控作用。结果显示,SH2B1基因在猪的6种组织中均有表达,且在脂肪组织中表达量最高,在肌肉组织中表达量最低。在猪生长发育各阶段背部脂肪中SH2B1基因均有表达,在前期(30和60 d)表达量较低,在中、后期(90、120和180 d)持续高表达,且显著高于前期表达量(P<0.05)。高、低背膘厚组背部脂肪中miR-276-3p与SH2B1基因均呈差异表达,且两者表达呈相反趋势,miR-276-3p在高背膘厚组中的表达量显著低于低背膘厚组(P<0.05),而SH2B1基因在高背膘厚组中的表达量却显著高于低背膘厚组(P<0.05)。miR-276-3p可通过靶向负调控SH2B1基因,影响猪背部脂肪的沉积。本试验结果为进一步深入研究猪背部脂肪沉积和背膘厚差异的分子机制提供参考。展开更多
目的探讨mi R-155基因敲除对大鼠动脉粥样硬化形成及对辛伐他汀治疗大鼠动脉粥样硬化疗效的影响。方法 mi R-155基因敲除雄性SD大鼠20只作为实验组,腹腔注射维生素D3,高脂饲料喂养进行大鼠动脉粥样硬化建模。8周后将实验组大鼠按完全随...目的探讨mi R-155基因敲除对大鼠动脉粥样硬化形成及对辛伐他汀治疗大鼠动脉粥样硬化疗效的影响。方法 mi R-155基因敲除雄性SD大鼠20只作为实验组,腹腔注射维生素D3,高脂饲料喂养进行大鼠动脉粥样硬化建模。8周后将实验组大鼠按完全随机抽样方法分为实验模型组和实验治疗组,每组10只,实验治疗组大鼠给予10 mg/kg辛伐他汀,实验模型组给予等量生理盐水。另取相同遗传背景、鼠龄和体重的雄性SD大鼠20只作为正常组,随机分为正常对照组和正常治疗组,每组10只,正常治疗组予以和实验治疗组大鼠同样的建模和给药,正常对照组普通饲料喂养,腹腔注射等量生理盐水。HE染色观察4组大鼠主动脉损伤;检测各组大鼠血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)和高密度脂蛋(HDL);q RT-PCR检测血管细胞粘附分子-1(VCAM-1)、白介素6(IL-6)、单核细胞趋化蛋白-1(MCP-1)m RNA在不同组别表达情况。结果与正常对照组相比,各模型组主动脉均见AS斑块形成。与正常对照组相比,正常模型组、实验模型组和辛伐他汀组大鼠TC、TG、LDLC水平均明显升高,正常模型组HDL明显下降,差异有统计学意义(P<0.05)。与正常模型组比较,实验模型组大鼠TC、TG、LDL水明显降低,HDL明显升高,差异有统计学意义(P<0.05)。与实验模型组相比,辛伐他汀组大鼠TC、TG、LDL均明显降低,HDL明显升高,差异有统计学意义(P<0.05)。与正常对照组相比,正常模型组、实验模型组和辛伐他汀组大鼠VCAM-1、IL-6和MCP-1的m RNA相对表达升高,差异有统计学意义(P<0.05)。与正常模型组比较,实验模型组大鼠VCAM-1、IL-6和MCP-1的m RNA表达降低,差异有统计学意义(P<0.05)。与实验模型组相比,辛伐他汀组大鼠VCAM-1、IL-6和MCP-1的m RNA表达降低,差异有统计学意义(P<0.05)。结论 mi R-155基因敲除可预防大鼠动脉粥样硬化形成,对辛伐他汀治疗大鼠动脉粥样硬化疗效产生有利的影响,可能为预防及治疗动脉粥样硬化提供方向。展开更多
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBSS00047(to PL)the National Natural Science Foundation of China,Nos.82072166(to PL),82071394(to XG)+4 种基金Science and Technology Planning Project of Tianjin,No.20YFZCSY00030(to PL)Science and Technology Project of Tianjin Municipal Health Commission,No.TJWJ2021QN005(to XG)Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-006ATianjin Municipal Education Commission Scientific Research Program Project,No.2020KJ164(to JZ)China Postdoctoral Science Foundation,No.2022M712392(to ZY).
文摘We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.
