文章摘要
卢 冰,费小明,汤 郁,陆 萍,李晓蕊.TNF⁃α预处理MC3T3⁃E1细胞后上调N⁃cadherin并影响骨髓血液生成[J].南京医科大学学报,2019,(7):949~954
TNF⁃α预处理MC3T3⁃E1细胞后上调N⁃cadherin并影响骨髓血液生成
TNF⁃α up⁃regulates N⁃cadherin and affects bone marrow hematopoiesis by pretreating MC3T3⁃E1 cells
投稿时间:2018-09-30  
DOI:10.7655/NYDXBNS20190701
中文关键词: 系统性红斑狼疮  骨髓微环境  MC3T3⁃E1  TNF⁃α  N⁃cadherin  p⁃Erk1/2
英文关键词: systemic lupus erythematosus  bone marrow microenvironment  MC3T3⁃E1  TNF⁃α  N⁃cadherin  p⁃Erk1/2
基金项目:国家自然科学基金(81571582,81202358);高层次卫生人才“六个一工程”拔尖人才科研项目(LGY2017101);江苏省卫生计生委科研课题(Z201512,H2018084)
作者单位
卢 冰 江苏大学附属医院血液科江苏 镇江 212001 
费小明 江苏大学附属医院血液科江苏 镇江 212001 
汤 郁 江苏大学附属医院风湿科江苏 镇江 212001 
陆 萍 江苏大学附属医院血液科江苏 镇江 212001 
李晓蕊 江苏大学附属医院血液科江苏 镇江 212001 
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中文摘要:
      目的:研究肿瘤环死因子α(tumor necrosis factor α,TNF?α)处理小鼠前成骨细胞株MC3T3?E1对其血液生成能力的影响及可能机制。方法:Western blot方法检测TNF?α处理MC3T3?E1细胞后,N?cadherin、p?Erk1/2和p?Akt的表达水平;将TNF?α预处理的MC3T3?E1细胞作为饲养层细胞,联合造血生长因子SCF、TPO和Flt3?配体,体外扩增分选的小鼠Sca?1(+)细胞7 d后,检测粒?单系集落形成单位(CFU?GM)、红系形成单位(BFU?E)和前B淋系形成单位(CFU?pre?B)。并检测Erk抑制剂FR180204对MC3T3?E1细胞N?cadherin和p?Erk水平的影响。结果:MC3T3?E1细胞经TNF?α预处理后,N?cadherin和p?Erk的表达上调,p?Akt没有明显变化。饲养层细胞联合造血生长因子体外扩增Sca?1(+)细胞7 d,与对照组比较,TNF?α预处理组中的总CFU、BFU?E及CFU?GM数目下降(P < 0.05),但CFU?pre?B数目明显升高(P < 0.05)。Erk抑制剂FR180204处理MC3T3?E1细胞可下调Erk的同时上调N?cadherin水平。结论:TNF?α可能通过影响骨髓微环境中造血支持细胞而间接影响血液生成和造血干细胞向各系列的分化;调节成骨细胞Erk1/2的磷酸化和N?cadherin的表达,可能是TNF?α影响骨髓血液生成的机制之一。
英文摘要:
      Objective:In this study,TNF?α treated mouse preosteoblast cell line MC3T3?E1 was used to investigate the effect of TNF? treated mouse preosteoblast cell line MC3T3?E1 on its hematopoiesis and its possible mechanism(s). Methods:MC3T3?E1 cells pretreated with TNF?α were used as feeder layer cells,combined with hematopoietic growth factor SCF,TPO and Flt3?ligand,and Sca?1(+)cells of mice were amplified and sorted in vitro for 7 days,and the granulocyte ? single?line colony formation unit(CFU?GM),red line formation unit(BFU?E)and pre?b line formation unit(CFU?pre?B)were detected. The effect of Erk inhibitor FR180204 on the levels of N?cadherin and p?Erk in MC3T3?E1 cells was also examined. Results:After pretreatment with TNF?α,the expression of N?cadherin was up?regulated,p?Erk was down?regulated,and p?Akt had no effect. The feeding layer cells combined with hematopoietic growth factor were amplified into Sca?1(+)cells in vitro for 7 days,compared with the control group,the number of total CFU,BFU?E and CFU?GM in TNF?α pretreatment group decreased(P < 0.05),but the number of CFU?pre?B increased significantly(P < 0.05). Erk inhibitor FR180204 treated MC3T3?E1 cells,it showed down?regulated Erk and up?regulated N?cadherin levels. Conclusion:TNF?α may indirectly affect production of the blood and differentiation of hematopoietic stem cells into various lines by affecting hematopoietic supporting cells in bone marrow microenvironment. Regulation of the phosphorylation of Erk1/2 and the expression of N?cadherin in osteoblasts may be one of the mechanisms by which TNF?α affects bone marrow hematopoiesis
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