PMPs通过CXCR2/Erk/NF-κB通路影响RA-FLS中RANKL和OPG表达的研究  

PMPs regulate the expressions of RANKL and OPG in RA-FLS via CXCR2/Erk/NF-κB pathway

作　　者：杨洁 王雯雯 张晨 邓子靖 周玮[3] 沈维干[4] 张育[1,4] YANG Jie;WANG Wenwen;ZHANG Chen;DENG Zijing;ZHOU Wei;SHEN Weigan;ZHANG Yu(Affiliated Subei Hospital of Yangzhou University,Yangzhou 225001,China;Nantong City No 1 People's Hospital/Second Affiliated Hospital of Nantong University,Nantong 226001,China;Affiliated Hospital of Yangzhou University,Yangzhou 225009,China;College of Medicine,Yangzhou University,Yangzhou 225009,China)

机构地区：[1]扬州大学附属苏北人民医院,江苏扬州225001 [2]南通市第一人民医院/南通大学第二附属医院,江苏南通226001 [3]扬州大学附属医院,江苏扬州225009 [4]扬州大学医学院,江苏扬州225009

出　　处：《扬州大学学报（农业与生命科学版）》2021年第1期41-46,57,共7页Journal of Yangzhou University：Agricultural and Life Science Edition

基　　金：国家自然科学基金资助项目(81470070、81771728)。

摘　　要：用不同浓度血小板微颗粒(PMPs,0、25、50μg·mL^(-1))分别处理RA-FLS,根据高通量基因芯片分析基因表达谱的改变,应用类风湿关节炎-成维样滑膜细胞(RT-qPCR)、Western blot和ELISA方法检测核因子κB受体活化因子(RANKL)和骨保护素(OPG)的表达;利用Western blot检测相关信号通路抑制剂对PMPs作用下类风湿关节炎-成纤维样滑膜细胞(RA-FLS)中核因子κB受体活化因子配体(RANKL)和OPG表达的影响。结果表明:PMPs可上调RA-FLS中RANKL表达,下调OPG表达;抑制NF-κB、CXCR2的活化能拮抗PMPs对RANKL和OPG表达的影响;PMPs上调RA-FLS中Erk的磷酸化水平时,IκB和NF-κB的磷酸化水平也随之上调。说明PMPs可能通过激活CXCR2/Erk/NF-κB信号通路上调RA-FLS中RANKL、下调OPG,参与类风湿关节炎的骨质破坏与重塑。RA-FLS was treated with 0,25,50μg·mL^(-1)PMPs.According to the gene expression profile detected by high throughput gene chip,the expression of RANKL and OPG was examined by RT-qPCR,Western blot and ELISA assays.Combined with signal pathway inhibitors,the effect of PMPs on expressions of RANKL and OPG in RA-FLS wsd evaluated by Western blot.The results showed that PMPs up-regulated the expression of RANKL and down-regulated the expression of OPG in RA-FLS.The results also demonstrated that the inhibition on NF-κB or CXCR2 activation antagonized the effect of PMPs on expressions of RANKL and OPG,and when PMPs induced phosphorylation of Erk in RA-FLS,phosphorylations of IκB and NF-κB were induced,too.Data from this study indicated that PMPs can up-regulate the expression of RANKL and down-regulate the expression of OPG in RA-FLS.The mechanism may be related to activating CXCR2/Erk/NF-κB signaling pathway,which may provide a new idea for the treatment of rheumatoid arthritis.

关 键 词：类风湿关节炎 成纤维样滑膜细胞 血小板微颗粒 RANKL OPG 

分 类 号：R593.22[医药卫生—内科学]