METTL3 promotes proliferation,migration,and secretion of inflammatory factors by mRNA m6A methylation in rheumatoid arthritis synovial fibroblasts
10.19405/j.cnki.issn1000-1492.2024.04.010
- VernacularTitle:METTL3通过mRNA m6A甲基化促进类风湿关节炎滑膜成纤维细胞增殖、迁移及分泌炎症因子
- Author:
Juan LI
1
;
Yangqing JIANG
;
Ruiming SHEN
;
Guoquan LI
;
Min WANG
;
Fenghuang XU
Author Information
1. 海南医学院第一附属医院风湿免疫科,海口 570102
- Keywords:
methyltransferase like 3;
methylation;
rheumatoid arthritis;
proliferation;
migration;
inflammatory factors
- From:
Acta Universitatis Medicinalis Anhui
2024;59(4):619-626
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and mechanism of methyltransferase-like 3(METTL3)on the pro-liferation,migration,and secretion of inflammatory factors by synovial fibroblasts from rheumatoid arthritis(RA).Methods The expression of METTL3 in synovial tissue(SF)from 25 patients with rheumatoid arthritis and 25 pa-tients with osteoarthritis was detected by RT-qPCR and immunohistochemistry,respectively.The concentration of RNA m6A was detected by ELISA.RA synovial fibroblasts were isolated and cultured,and divided into NC(nor-mal control)group,hi-METTL3(overexpression of METTL3)group,si-METTL3(knock-down METTL3)group,and STM2457(METTL3 specific inhibitor)intervention group.Cell proliferation was detected by CCK-8 method.Apoptosis was detected by flow cytometry.And the concentrations of interleukin-6(IL-6),interleukin-17A(IL-17A),receptor activator of nuclear factor-kappa B ligand(RANKL),and osteoprotegerin(OPG)in the superna-tant of cell culture were detected by ELISA.Results Compared with synovial tissue of osteoarthritis,the expres-sion of mRNA m6A and METTL3 in synovial tissue of RA significantly increased(P<0.05).After overexpression of METTL3,the expression of m6A in synovial fibroblasts increased.The proliferation and migration abilities of SF in hi-METTL3 group were significantly improved,and their apoptosis did not change significantly.The secretion of cytokines IL-6 and RANKL of SF in hi-METTL3 group significantly increased,while the OPG significantly de-creased(P<0.05).After interfering with METTL3 expression,the expression of m6A in synovial fibroblasts de-creased.Cell proliferation and migration of SF in siMETTL3 group significantly decreased.The secretion of cyto-kines IL-6 and RANKL significantly decreased,and OPG significantly increased(P<0.05).After intervention with METTL3 inhibitor STM2457,the proliferation and migration of synovial fibroblasts were significantly reduced,and the secretion of cytokines IL-6 and RANKL significantly reduced,and OPG significantly increased(P<0.05).There was no significant difference in the expression of IL-17A among each group.Conclusion METTL3 may promote the proliferation and migration of RA synovial fibroblasts,enhance the expression of IL-6 and RANKL,and inhibit the expression of OPG through RNA m6A methylation modification.
