title: Fibroblast growth factor 21 (FGF21) ameliorates collagen-induced arthritis through modulating oxidative stress and suppressing nuclear factor-kappa B pathway.
abstract: It has been demonstrated that circulating FGF21 levels are elevated in the serum and synovial fluid of patients with rheumatoid arthritis (RA). The aim of this study is to investigate efficacy of FGF21 for treatment of RA and the molecular mechanisms of the therapeutic effect on collagen-induced arthritis (CIA). Mice with CIA were subcutaneously administered with FGF21 (5, 2 or 1mg·kg(-1)·d(-1)), IL-1β antibody (5mg·kg(-1)·d(-1)), IL-17A antibody (5mg·kg(-1)·d(-1)) and dexamethasone (DEX) (1mg·kg(-1)·d(-1)), respectively. The effects of treatment were determined by arthritis severity score, histological damage and cytokine production. The activation of NF-κB was analyzed by Western blotting. We also detected the levels of oxidative stress parameters. Our results showed that FGF21 had beneficial effects on clinical symptom and histological lesion of CIA mice. Similar to antibody and DEX, FGF21 treatment alleviated the severity of arthritis by reducing humoral and cellular immune responses and down-regulating the expression of pro-inflammatory cytokines. FGF21 treatment also reduced the expression of TNF-α, IL-1β, IL-6, IFN-γ and MMP-3 and increased level of IL-10 in the spleen tissue or the plasma of CIA mice in a dose-dependent manner. Furthermore, FGF21 inhibited IκBα degradation and NF-κB p65 nuclear translocation and induced significant changes of oxidative stress parameters (MDA, SOD, CAT, GSH-PX and GSH) in the plasma. FGF21 exerts therapeutic efficacy for RA through antioxidant reaction and inhibiting NF-κB inflammatory pathway. This study provides evidence that FGF21 may be a promising therapeutic agent for RA patients.
authors.affiliation: Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Yinhang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China; Harbin University of Commerce, Harbin 150028, China.
authors.forename: Siming
authors.initials: S
authors.lastname: Li
authors.affiliation: Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Yaonan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Guiyou
authors.initials: G
authors.lastname: Tian
authors.affiliation: Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Fuliang
authors.initials: F
authors.lastname: Bai
authors.affiliation: Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China; Key Laboratory of Agricultural Biological Functional Gene, Harbin 150030, China.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Harbin Medical University, The First Affiliated Hospital, Nangang District, 150001 Harbin, China.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China; Key Laboratory of Agricultural Biological Functional Gene, Harbin 150030, China. Electronic address: renguiping@126.com.
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150030, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China; Key Laboratory of Agricultural Biological Functional Gene, Harbin 150030, China. Electronic address: deshanli@163.com.
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage / Q000009:adverse effects; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D005346:Fibroblast Growth Factors / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007165:Immunosuppression Therapy; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019138:Antibodies, Blocking; D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D003907:Dexamethasone; D019278:Matrix Metalloproteinase 3
keywords: Collagen-induced arthritis; FGF21; Inflammation; NF-κB; Oxidative stress; Rheumatoid arthritis