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

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 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. Conclusion DVL2 can increase the apoptosis rate of RA-FLS through inhibiting the JAK-STAT pathway and its downstream anti-apoptotic gene. Key words: Rheumatoid arthritis; Dishevelled; Fibroblast-like synoviocytes; Apoptosis; JAK-STAT pathway