巢乱蛋白2及JAK-STAT通路对类风湿关节炎成纤维样滑膜细胞凋亡的影响  

Effect of Dishevelled 2 on apoptosis in rheumatoid arthritis fibroblast-like synoviocytes through inhibiting JAK-STAT pathway

作　　者：刘兴振 高颖 祝春华[1] 綦柯 徐霞 赵东宝 Liu Xingzhen;Gao Ying;Zhu Chunhna;Qi Ke;Xu Xia;Zhao Dongbao(Army Convalescence Area, Hangzhou Sanatorium of People＇s Liberation Army, Hangzhou 310007, China)

机构地区：[1]解放军杭州疗养院直属院区,杭州310007 [2]解放军海军军医大学附属长海医院风湿免疫科 [3]解放军海军军医大学附属长海医院关节外科

出　　处：《中华医学杂志》2018年第15期1189-1193,共5页National Medical Journal of China

基　　金：国家自然科学基金（81471607,81671595,81273284）

摘　　要：目的探讨巢乱蛋白（DVL）是否通过JAK-STAT通路来调控类风湿关节炎成纤维样滑膜细胞（RA-FLS）的凋亡。方法将DVL2过表达慢病毒转染入RA-FLS后通过流式细胞仪检测细胞的凋亡率；通过RNA-seq检测DVL2对RA-FLS信号通路的影响，并利用RT-PCR对通路上的重点基因和下游的抗凋亡基因进行验证。结果与空载慢病毒对照组（Control）相比，DVL2可以明显增加MH7A细胞的凋亡率（3.2%±2.2%及25.7%±4.5%）。RNA-seq结果显示，DVL2可以下调JAK-STAT通路中的相关基因，利用RT-PCR进一步验证发现DVL2可以抑制JAK2、Stat1和Stat2基因的表达，加入肿瘤坏死因子（TNF）-α刺激后DVL2可以明显抑制JAK2和Stat2基因的表达但对Stat1的抑制作用不明显；DVL2可以抑制Bcl-xL基因的表达，加入TNF-α刺激后对Bcl-2和Bcl-xL均有明显抑制作用。结论DVL2可以抑制JAK-STAT通路及其下游的抗凋亡基因的表达促进RA-FLS的凋亡。Objective To investigate if Dishevelled 2 （DVL2） regulates the apoptosis of rheumatoid arthritis fibroblast-like synoviocytes （RA-FLS） via the JAK-STAT pathway. Methods DVL2 overexpressed lentivirus was transfected into RA-FLS and the apoptosis rate was detected by flow cytometry. The effect of DVL2 on RA-FLS signaling pathway was detected by RNA-seq, and then the key genes were verified by RT-PCR. Results Compared with the control group, DVL2 significantly increased the apoptosis rate of MHTA （3.2% ±2. 2% vs 25.7% ±4. 5% ）. RNA-seq results showed that DVL2 down-regulated the JAK-STAT pathway. The results of RT-PCR showed that DVL2 inhibited the gene expression of JAK2, Statl, and Stat2; DVL2 still inhibited the gene expression of JAK2 and Stat2 but not Statl after TNF-astimulation. DVL2 inhibited the gene expression of Bcl-xL, and the gene expression of Bcl-2 and Bcl-xL after TNF-oL stimulation. Conclusion DVL2 can increase the apoptosis rate of RA-FLS through inhibiting the JAK-STAT pathway and its downstream anti-apoptotic gene.

关 键 词：类风湿关节炎 DISHEVELLED 成纤维样滑膜细胞 凋亡 JAK-STAT通路 

分 类 号：R593.22[医药卫生—内科学]