神经调节蛋白1,3和4促胶质瘤细胞迁移比较研究  

Comparison of NRG1,3 and 4 in promoting glioma cell migration

作　　者：乔新宇 易三军 赵炜疆 QIAO Xin-yu;YI San-jun;ZHAO Wei-jiang(Wuxi Medical College, Jiangnan University, Wuxi Jiangsu 214122, China;Center for Neuroscience, Shantou University Medical College, Shantou Guangdong 515041, China)

机构地区：[1]江南大学无锡医学院,江苏无锡214122 [2]汕头大学医学院神经科学中心,广东汕头515041

出　　处：《中国药理学通报》2021年第10期1396-1401,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上项目(No 81471279,81171138)。

摘　　要：目的研究不同神经调节蛋白亚型NRG1、NRG3和NRG4对不同人胶质瘤细胞迁移的影响。方法U-87 MG、U251及SHG44细胞划痕后,给予浓度0、2、5、10 nmol·L^(-1)重组人源神经调节蛋白。于划痕后0-48 h范围测量细胞迁移率。使用GEPIA数据库分析低级别胶质瘤和胶质母细胞瘤样本中神经调节蛋白及受体表达水平变化。结果rNRG1β、rNRG3β和rNRG4β均可不同程度促进U-87 MG、U251及SHG44细胞迁移。rNRG3β和rNRG4β的促迁移作用弱于rNRG1β。低级别胶质瘤样本中NRG1和NRG4表达水平明显低于正常对照组,ErbB2、ErbB3和ErbB4表达水平高于正常对照组;胶质母细胞瘤样本中NRG1、NRG3和NRG4表达水平显著低于正常对照组,而ErbB2表达水平显著高于正常对照组,ErbB3和ErbB4表达水平低于正常对照组。结论NRG1、NRG3和NRG4均可不同程度促进胶质瘤细胞迁移。3种NRG亚型在胶质瘤浸润和转移中的作用存在差异性,其原因可能系相应ErbB受体表达水平差异。Aim To study the effect of different neuregulin subtypes on the migration of human glioma cells.Methods Recombinant human NRGs,including rNRG1β,rNRG3β,and rNRG4β,were individually administered to U-87MG,U251 cells and SHG44 cells at doses of 0,2,5 and 10 nmol·L^(-1),before which a uniform wound scratch was induced.The migration rate of scratched U-87 MG cells was measured at the time points of 0 h,6 h,12 h,and 24 h.And the migration rate was measured at 0 h,12 h,24 h and 48 h for scratched U251 cells,and for scratched SHG44 cells at 0 h,24 h and 48 h.By using GEPIA database analysis,the gene expression of NRG1,NRG3 and NRG4,as well as that of ErbB2,ErbB3 and ErbB4 in low grade glioma(LGG)and glioblastoma multiforme(GBM)samples were respectively compared with those in normal control group.Results The rNRGs we tested could differentially promote the migration of glioma/glioblastoma cells.However,the migration promoting effect of rNRG3βand rNRG4βwas relatively weaker than that of rNRG1β.The expression levels of NRG1 and NRG4 in LGG samples were significantly lower than those in normal control group(P<0.05).In addition,ErbB2,ErbB3 and ErbB4 expression levels were higher than those in normal control group.Although the expression levels of NRG1,NRG3 and NRG4 in GBM samples were significantly lower than those in normal control group(P<0.05),the expression levels of ErbB2 were significantly higher(P<0.05).In contrast,the expression levels of ErbB3 and ErbB4 were lower than those in normal control group.Conclusions NRG1,NRG3 and NRG4 can all promote glioma cell migration to different degrees,with the most obvious effect observed in rNRG1β-treated cells.These data suggest differential roles of NRG subtypes in glioma invasion and metastasis,which is related to the differential expression of NRGs and corresponding ErbB receptors in LGG and GBM.

关 键 词：胶质瘤 神经调节蛋白 U-87MG U251 SHG44 迁移 GEPIA 

分 类 号：R341[医药卫生—基础医学] R730.246