title: Role of protein arginine methyltransferase 5 in inflammation and migration of fibroblast-like synoviocytes in rheumatoid arthritis.
abstract: To probe the role of protein arginine methyltransferase 5 (PRMT5) in regulating inflammation, cell proliferation, migration and invasion of fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). FLSs were separated from synovial tissues (STs) from patients with RA and osteoarthritis (OA). An inhibitor of PRMT5 (EPZ015666) and short interference RNA (siRNA) against PRMT5 were used to inhibit PRMT5 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. FLSs proliferation was detected by BrdU incorporation. Increased PRMT5 was discovered in STs and FLSs from patients with RA. In RA FLSs, the level of PRMT5 was up-regulated by stimulation with IL-1β and TNF-α. Inhibition of PRMT5 by EPZ015666 and siRNA-mediated knockdown reduced IL-6 and IL-8 production, and proliferation of RA FLSs. In addition, inhibition of PRMT5 decreased in vitro migration and invasion of RA FLSs. Furthermore, EPZ015666 restrained the phosphorylation of IκB kinaseβ and IκBα, as well as nucleus transsituation of p65 as well as AKT in FLSs. PRMT5 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 PRMT5 to prevent synovial inflammation and destruction might be a promising therapy for RA.
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Dongying
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Mingcheng
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Hanshi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Liuqin
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Yang
mesh_terms: D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010003:Osteoarthritis / Q000201:enzymology / Q000473:pathology; D011484:Protein-Arginine N-Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000070918:Synoviocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D018836:Inflammation Mediators; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase
keywords: fibroblast-like synoviocytes; inflammation; migration; protein arginine methyltransferases 5; rheumatoid arthritis