葡萄糖代谢异常参与RA发病的研究进展
摘要
RA是一种全身性自身免疫病,主要侵犯关节滑膜,致残率极高,但发病机制至今未明。近年来,随着免疫代谢研究领域的兴起,RA发病与细胞代谢的关系正被广泛研究。文章主要概括了葡萄糖代谢异常参与RA发病的研究进展,以关节滑膜细胞与CD4~+T细胞为主要研究对象,从糖酵解和磷酸戊糖2个主要代谢途径分别展开分析。这一研究进展的归纳有利于从免疫代谢角度认识RA的发病机制,为该病的临床治疗提供新的思路。
引文
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[27] Tsokos GC.Metabolic control of arthritis:Switch pathways to treat[J].Sci Transl Med,2016,8(331):331fs8.
[2] Balogh E,Veale DJ,McGarry T,et al.Oxidative stress impairs energy metabolism in primary cells and synovial tissue of patients with rheumatoid arthritis[J].Arthritis Res Ther,2018,20(1):95.
[3] McGarry T,Biniecka M,Gao W,et al.Resolution of TLR2-induced inflammation through manipulation of metabolic pathways in Rheumatoid Arthritis[J].Sci Rep,2017,7:43165.
[4] Garcia-Carbonell R,Divakaruni AS,Lodi A,et al.Critical role of glucose metabolism in rheumatoid arthritis fibroblast-like synoviocytes[J].Arthritis Rheumatol,2016,68(7):1614-1626.
[5] Chang X,Wei C.Glycolysis and rheumatoid arthritis[J].Int J Rheum Dis,2011,14(3):217-222.
[6] 何东仪,钟丽民,沈杰,等.葡萄糖6-磷酸异构酶检测在类风湿关节炎中的意义[J].现代免疫学,2008,28(4):326-330.
[7] Bustamante MF,Oliveira PG,Garcia-Carbonell R,et al.Hexokinase 2 as a novel selective metabolic target for rheumatoid arthritis[J].Ann Rheum Dis,2018,77(11):1-8.
[8] Yang Z,Fujii H,Mohan SV,et al.Phosphofructokinase deficiency impairs ATP generation,autophagy,and redox balance in rheumatoid arthritis T cells[J].J Exp Med,2013,210(10):2119-2134.
[9] Ahn JK,Kim S,Hwang J,et al.GC/TOF-MS-based metabolomic profiling in cultured fibroblast-like synoviocytes from rheumatoid arthritis[J].Jt Bone Spine,2016,83(6):707-713.
[10] Zou Y,Zeng S,Huang M,et al.Inhibition of 6-phosphofructo-2-kinase suppresses fibroblast-like synoviocytes-mediated synovial inflammation and joint destruction in rheumatoid arthritis[J].Br J Pharmacol,2017,174(9):893-908.
[11] Roberts DJ,Miyamoto S.Hexokinase II integrates energy metabolism and cellular protection:Akting on mitochondria and TORCing to autophagy[J].Cell Death Differ,2015,22(2):248-257.
[12] Shi LZ,Wang R,Huang G,et al.HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells[J].J Exp Med,2011,208(7):1367-1376.
[13] Bodur C,Karakas B,Timucin AC,et al.AMP-activated protein kinase couples 3-bromopyruvate-induced energy depletion to apoptosis via activation of FoxO3a and upregulation of proapoptotic Bcl-2 proteins[J].Mol Carcinog,2016,55(11):1584-1597.
[14] Okano T,Saegusa J,Nishimura K,et al.3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17/Treg cell differentiation and suppressing dendritic cell activation[J].Sci Rep,2017,7:42412.
[15] Wang R,Dillon CP,Shi LZ,et al.The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation[J].Immunity,2011,35(6):871-882.
[16] Hsieh AL,Walton ZE,Altman BJ,et al.MYC and metabolism on the path to cancer[J].Semin Cell Dev Biol,2015,43:11-21.
[17] Stine ZE,Walton ZE,Altman BJ,et al.MYC,metabolism,and cancer[J].Cancer Discov,2015,5(10):1024-1039.
[18] Lee MS,Moon EJ,Lee SW,et al.Angiogenic activity of pyruvic acid in in vivo and in vitro angiogenesis models[J].Cancer Res,2001,61(8):3290-3293.
[19] Haas R,Smith J,Rocher-Ros V,et al.Lactate regulates metabolic and pro-inflammatory circuits in control of T cell migration and effector functions[J].PLoS Biol,2015,13(7):e1002202.
[20] Gatenby RA,Gillies RJ.Why do cancers have high aerobic glycolysis?[J].Nat Rev Cancer,2004,4(11):891-899.
[21] Hua S,Dias TH.Hypoxia-inducible factor (HIF) as a target for novel therapies in rheumatoid arthritis[J].Front Pharmacol,2016,7:184.
[22] Palazon A,Goldrath AW,Nizet V,et al.HIF transcription factors,inflammation,and immunity[J].Immunity,2014,41(4):518-528.
[23] Weyand CM,Goronzy JJ.Immunometabolism in early and late stages of rheumatoid arthritis[J].Nat Rev Rheumatol,2017,13(5):291-301.
[24] Yang Z,Shen Y,Oishi H,et al.Restoring oxidant signaling suppresses proarthritogenic T cell effector functions in rheumatoid arthritis[J].Sci Transl Med,2016,8(331):331ra38.
[25] Klarer AC,O'Neal J,Imbert-Fernandez Y,et al.Inhibition of 6-phosphofructo-2-kinase (PFKFB3) induces autophagy as a survival mechanism[J].Cancer Metab,2014,2(1):2.
[26] Yang Z,Goronzy JJ,Weyand CM.The glycolytic enzyme PFKFB3/phosphofructokinase regulates autophagy[J].Autophagy,2014,10(2):382-383.
[27] Tsokos GC.Metabolic control of arthritis:Switch pathways to treat[J].Sci Transl Med,2016,8(331):331fs8.