Open AccessRole of protein arginine methyltransferase 5 in inflammation and migration of fibroblast‐like synoviocytes in rheumatoid arthritis
Author(s) -
Chen Dongying,
Zeng Shan,
Huang Mingcheng,
Xu Hanshi,
Liang Liuqin,
Yang Xiuyan
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13020
Subject(s) - protein arginine methyltransferase 5 , protein kinase b , inflammation , gene knockdown , chemistry , cell migration , cancer research , signal transduction , cell growth , microbiology and biotechnology , immunology , methyltransferase , in vitro , apoptosis , medicine , biology , biochemistry , methylation , gene
To probe the role of protein arginine methyltransferase 5 ( PRMT 5) in regulating inflammation, cell proliferation, migration and invasion of fibroblast‐like synoviocytes ( FLS s) from patients with rheumatoid arthritis ( RA ). FLS s were separated from synovial tissues ( ST s) from patients with RA and osteoarthritis ( OA ). An inhibitor of PRMT 5 ( EPZ 015666) and short interference RNA (si RNA ) against PRMT 5 were used to inhibit PRMT 5 expression. The standard of protein was measured by Western blot or immunofluorescence. The excretion and genetic expression of inflammatory factors were, respectively, estimated by enzyme‐linked immunosorbent assay ( ELISA ) and real‐time polymerase chain reaction ( PCR ). Migration and invasion in vitro were detected by Boyden chamber assay. FLS s proliferation was detected by BrdU incorporation. Increased PRMT 5 was discovered in ST s and FLS s from patients with RA . In RA FLS s, the level of PRMT 5 was up‐regulated by stimulation with IL ‐1β and TNF ‐α. Inhibition of PRMT 5 by EPZ 015666 and si RNA ‐mediated knockdown reduced IL ‐6 and IL ‐8 production, and proliferation of RA FLS s. In addition, inhibition of PRMT 5 decreased in vitro migration and invasion of RA FLS s. Furthermore, EPZ 015666 restrained the phosphorylation of IκB kinaseβ and IκBα, as well as nucleus transsituation of p65 as well as AKT in FLS s. PRMT 5 regulated the production of inflammatory factors, cell proliferation, migration and invasion of RA FLS , which was mediated by the NF ‐κB and AKT pathways. Our data suggested that targeting PRMT 5 to prevent synovial inflammation and destruction might be a promising therapy for RA .