title: Dishevelled2 promotes apoptosis and inhibits inflammatory cytokine secretion in rheumatoid arthritis fibroblast-like synoviocytes through crosstalk with the NF-κB pathway.
abstract: Dishevelled (Dvl) not only links the canonical Wnt and non-canonical Wnt pathways but can also crosstalk with other pathways. As there is no systematic study to date on Dvl in rheumatoid arthritis (RA), we explored the impact of Dvl2 on proliferation and inflammatory cytokine secretion in RA fibroblast-like synoviocytes (FLSs). Expression of Dvl2 in RA synovial tissue and RA-FLSs was measured. Dvl2 was overexpressed in collagen-induced arthritis rats and human RA-FLSs,. the apoptosis and secretion of inflammatory cytokines were observed. Genetic changes and corresponding mechanisms caused by overexpressing Dvl2 in RA-FLSs were assessed. Dvl2 was found to be overexpressed in RA synovial tissue and RA-FLSs. Overexpression of Dvl2 increased apoptosis and inhibited inflammatory cytokine secretion by RA-FLSs in vivo and in vitro, and Dvl2 inhibited expression of anti-apoptotic and inflammatory genes. One possible mechanism is that Dvl2 decreases the nuclear translocation of P65 and inhibits its ability to bind to the promoters of NF-κB target genes. Our findings reveal an underappreciated role of Dvl2 in regulating inflammation and RA-FLS apoptosis and provide insight into crosstalk between the Wnt and nuclear factor-κB (NF-κB) pathways.
authors.affiliation: Department of Rheumatology and Immunology, Changhai Hospital, The Second Military Medical University, Shanghai, China.|Army Convalescence Area, Hangzhou Sanatorium of People's Liberation Army, Hangzhou, China.
authors.forename: Xing Zhen
authors.initials: XZ
authors.lastname: Liu
authors.affiliation: Army Convalescence Area, Hangzhou Sanatorium of People's Liberation Army, Hangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Joint Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Qi
authors.affiliation: Experimental Center, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Shu Peng
authors.initials: SP
authors.lastname: Liu
authors.affiliation: Department of Joint Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Wei Dong
authors.initials: WD
authors.lastname: Xu
authors.affiliation: Department of Rheumatology and Immunology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Rheumatology and Immunology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Xiao Dan
authors.initials: XD
authors.lastname: Gu
authors.affiliation: Department of Joint Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Chen Guang
authors.initials: CG
authors.lastname: Bai
authors.affiliation: Department of Rheumatology and Immunology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Ye Qing
authors.initials: YQ
authors.lastname: Shi
authors.affiliation: Department of Rheumatology and Immunology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Lan Ling
authors.initials: LL
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Immunology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Dong Bao
authors.initials: DB
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D000072261:Dishevelled Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D007249:Inflammation / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020239:Receptor Cross-Talk / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D000070918:Synoviocytes / Q000378:metabolism*
chemical_list: D016207:Cytokines; D000072261:Dishevelled Proteins; D016328:NF-kappa B
keywords: Immune response; Immunity; Immunology and Microbiology Section; apoptosis; dishevelled2; inflammation; rheumatoid arthritis; synovial fibroblast