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STAT4基因敲除通过miR-9促进泡沫细胞形成及动脉粥样硬化 被引量:7
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作者 许莉莉 丁素玲 +5 位作者 张伟伟 朱小伟 朱宝玲 邹云增 杨向东 葛均波 《中国动脉硬化杂志》 CAS 2020年第5期410-420,共11页
目的探究动脉粥样硬化斑块发生发展过程中信号转导与转录激活因子4(STAT4)信号通路在巨噬细胞分化及泡沫细胞形成中的作用及调控机制。方法将STAT4基因敲除(STAT4-/-)小鼠与载脂蛋白E基因敲除(ApoE-/-)小鼠进行杂交,筛选出ApoE/STAT4纯... 目的探究动脉粥样硬化斑块发生发展过程中信号转导与转录激活因子4(STAT4)信号通路在巨噬细胞分化及泡沫细胞形成中的作用及调控机制。方法将STAT4基因敲除(STAT4-/-)小鼠与载脂蛋白E基因敲除(ApoE-/-)小鼠进行杂交,筛选出ApoE/STAT4纯合子双基因敲除(DKO)小鼠,研究新型动脉粥样硬化相关小鼠模型的易感性和机制。将3月龄小鼠分为野生型(WT)、STAT4-/-、ApoE-/-、DKO共4组,经过12周高脂胆固醇饮食喂养,分别采用油红O染色及石蜡切片HE/Masson染色检测主动脉斑块形成情况。采用流式细胞术分析小鼠外周血、骨髓及脾脏髓系细胞各亚群比例。从小鼠骨髓分离CD11b+髓系细胞进行体外培养,采用巨噬细胞集落刺激因子(M-CSF)进行诱导,流式分析巨噬细胞不同亚型分化情况。采用实时定量聚合酶链反应(PCR)及Western blot分别检测基因表达水平及蛋白水平。结果ApoE-/-小鼠动脉粥样硬化斑块局部的CD11b+细胞中可检测到STAT4表达。ApoE-/-及DKO小鼠经12周高脂喂养,油红O染色阳性的主动脉斑块主要分布在主动脉根部至髂动脉分叉处,DKO小鼠的斑块较ApoE-/-小鼠明显增多;HE及Masson染色显示DKO小鼠的主动脉斑块较ApoE-/-小鼠具有更薄的纤维帽及更大的脂质核心,且斑块中的纤维更稀疏,排列也相对更紊乱。体外细胞实验显示STAT4基因敲除可促进CD11b+Gr-1+未成熟髓系细胞的异常动员、巨噬细胞的M1极化以及泡沫化。STAT4基因缺失通过磷酸肌醇3激酶(PI3K)/丝氨酸苏氨酸激酶(Akt)/核因子κB(NF-κB)通路下调miR-9的表达,上调酰基辅酶A胆固醇酰基转移酶(ACAT-1)表达,进而促进巨噬细胞的脂质蓄积及泡沫细胞形成,最终加速动脉粥样硬化斑块的发生发展。结论STAT4通过调控免疫炎症反应及脂质代谢,在巨噬细胞分化及泡沫细胞形成过程中发挥关键作用。STAT4相关信号通路可作为未来动脉粥样硬化性疾病的潜在治疗靶点。 展开更多
关键词 动脉粥样硬化 巨噬细胞 泡沫细胞 STAT4通路
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心肌样软基质与玻璃硬基质对CD34^+细胞向内皮系细胞分化的影响 被引量:1
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作者 张书宁 马鑫 +8 位作者 杨文龙 董震 姚康 朱宏 王鹏 邹云增 杨向东 孙爱军 葛均波 《中国动脉硬化杂志》 CAS 2019年第6期461-467,共7页
目的比较心肌组织样软基质与玻璃硬基质对小鼠骨髓CD34^+及CD34^-细胞亚群向内皮系细胞分化的差异。方法利用原子力显微镜检测正常Balb/c小鼠心肌组织硬度(弹性模量≈15kPa),采用聚丙烯酰胺凝胶制备心肌样软培养基底铺于玻璃培养皿中,... 目的比较心肌组织样软基质与玻璃硬基质对小鼠骨髓CD34^+及CD34^-细胞亚群向内皮系细胞分化的差异。方法利用原子力显微镜检测正常Balb/c小鼠心肌组织硬度(弹性模量≈15kPa),采用聚丙烯酰胺凝胶制备心肌样软培养基底铺于玻璃培养皿中,利用密度梯度离心法及免疫磁珠分选法收集小鼠骨髓CD34^+及CD34^-细胞,分别于心肌样软基底及玻璃硬基底培养皿(弹性模量>1GPa)中进行细胞培养,培养7天后,利用激光共聚焦显微镜观测内皮细胞系表面标志物、细胞形态及细胞骨架。结果在两个硬度培养体系中,CD34^+细胞均表现出较CD34^-细胞更高的乙酰化低密度脂蛋白(ac-LDL)/荆豆凝集素I(UEA-1)双阳性比例(P<0.01),以及更高的CD31、vWF、Flk-1和VE-cadherin等内皮细胞系标记物表达(P<0.05)。就两种细胞亚型的分化差异而言,心肌样软基质较玻璃硬基质表现出更高的细胞分化诱导效率,这可能与软基质上CD34^+细胞表现出更为浓集的黏着斑和F-actin有关。结论与玻璃硬基质相比,心肌样软基质能更为有效的诱导CD34^+细胞亚群向内皮系分化;软基底培养体系是一种更佳的探讨细胞生物行为的培养体系。 展开更多
关键词 心肌组织 CD34 细胞分化 细胞外基质
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Activation of histamine/H R signaling pathway promotes cardiac differentiation and maturation of human induced pluripotent stem cells
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作者 Zhu Xiaowei Ding Suling +4 位作者 Zhu Baoling Wang Xiangfei zou yunzeng Yang Xiangdong Ge Junbo 《解剖学杂志》 CAS 2021年第S01期224-225,共2页
The efficiency and quality of human induced pluripotent stem cell-derived cardiomyocytes(hiPSC CMs)is crucial for regenerative medicine,disease modeling,drug screening and the study of the development events during ca... The efficiency and quality of human induced pluripotent stem cell-derived cardiomyocytes(hiPSC CMs)is crucial for regenerative medicine,disease modeling,drug screening and the study of the development events during cardiac specification.However,their applications have been hampered by the differentiation efficiency,poor maturation and high interline variability.Recent studies have reported that histamine plays important roles in hema topoietic stem cell proliferation and neutrophil maturation.However,its roles in cardiovascular tissue regeneration have not been thoroughly investigated.In the current study,we identified a novel physiological function of the histamine/histamine 1 receptor(H,R)signal in regulating the differentiation of hiPSC-CMs and heart development. 展开更多
关键词 CARDIAC CARDIOVASCULAR thoroughly
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miR-210 over-expression enhances mesenchymal stem cell survival in an oxidative stress environment through antioxidation and c-Met pathway activation 被引量:11
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作者 XU JianFeng HUANG ZheYong +7 位作者 LIN Li FU MingQiang GAO YanHua SHEN YunLi zou yunzeng SUN AiJun QIAN JuYing GE JunBo 《Science China(Life Sciences)》 SCIE CAS 2014年第10期989-997,共9页
microRNA-210(miR-210)has generally been reported to be associated with cell survival under hypoxia.However,there are few data regarding the role of miR-210 in the survival of mesenchymal stem cells(MSCs)under oxidativ... microRNA-210(miR-210)has generally been reported to be associated with cell survival under hypoxia.However,there are few data regarding the role of miR-210 in the survival of mesenchymal stem cells(MSCs)under oxidative stress conditions.Thus,we sought to investigate whether miR-210 over-expression could protect MSCs against oxidative stress injury and what the primary mechanisms involved are.The results showed that over-expression of miR-210 significantly reduced the apoptosis of MSCs under oxidative stress,accompanied by obvious increases in cell viability and superoxide dismutase activity and remarkable decreases in malonaldehyde content and reactive oxygen species production,resulting in a noticeable reduction of apoptotic indices when compared with the control.Moreover,the above beneficial effects of miR-210 could be significantly reduced by c-Met pathway repression.Collectively,these results showed that miR-210 over-expression improved MSC survival under oxidative stress through antioxidation and c-Met pathway activation,indicating the potential development of a novel approach to enhance the efficacy of MSC-based therapy for injured myocardium. 展开更多
关键词 microRNAs stem cells oxidative stress signal transduction
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