[Dishevelled 2通过抑制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].

作者信息

Liu X Z, Gao Y, Zhu C H, Qi K, Xu X, Zhao D B

机构信息

Army Convalescence Area, Hangzhou Sanatorium of People's Liberation Army, Hangzhou 310007, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2018 Apr 17;98(15):1189-1193. doi: 10.3760/cma.j.issn.0376-2491.2018.15.013.

DOI:10.3760/cma.j.issn.0376-2491.2018.15.013

PMID:29690734

Abstract

To investigate if Dishevelled 2 (DVL2) regulates the apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) via the JAK-STAT pathway. 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. Compared with the control group, DVL2 significantly increased the apoptosis rate of MH7A (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, Stat1, and Stat2; DVL2 still inhibited the gene expression of JAK2 and Stat2 but not Stat1 after TNF-α stimulation.DVL2 inhibited the gene expression of Bcl-xL, and the gene expression of Bcl-2 and Bcl-xL after TNF-α stimulation. DVL2 can increase the apoptosis rate of RA-FLS through inhibiting the JAK-STAT pathway and its downstream anti-apoptotic gene.

摘要

探讨Dishevelled 2（DVL2）是否通过JAK-STAT途径调节类风湿关节炎成纤维样滑膜细胞（RA-FLS）的凋亡。将DVL2过表达慢病毒转染至RA-FLS中，通过流式细胞术检测凋亡率。通过RNA测序检测DVL2对RA-FLS信号通路的影响，然后通过RT-PCR验证关键基因。与对照组相比，DVL2显著提高了MH7A的凋亡率（3.2%±2.2%对25.7%±4.5%）。RNA测序结果显示DVL2下调了JAK-STAT途径。RT-PCR结果显示DVL2抑制JAK2、Stat1和Stat2的基因表达；TNF-α刺激后，DVL2仍抑制JAK2和Stat2的基因表达，但不抑制Stat1。DVL2抑制Bcl-xL的基因表达，以及TNF-α刺激后Bcl-2和Bcl-xL的基因表达。DVL2可通过抑制JAK-STAT途径及其下游抗凋亡基因来提高RA-FLS的凋亡率。