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
- Author:
Juan Li
1
;
Yangqing Jiang
1
;
Ruiming Shen
1
;
Guoquan Li
1
;
Min Wang
1
;
Fenghuang Xu
1
Author Information
1. Dept of Rheumatology and Immunology , First Afiliated Hospital of Hainan Medical University , Haikou 570102
- Publication Type:Journal Article
- 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 .
- Full text:2024070222252404081METTL3通过mRNA_...胞增殖、迁移及分泌炎症因子_李娟.pdf
