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南京医科大学学报(自然科学版)                                  第46卷第4期
               ·598 ·                     Journal of Nanjing Medical University(Natural Sciences)   2026年4月


             ·综      述·

              PFKM通过经典与非经典途径调控巨噬细胞功能的研究进展



              姚   晨 ,杨 晶 ,潘宇晨          1,2*
                     1,2
                              1,2
               徐州医科大学基础医学院病原生物学与免疫学教研室,江苏省免疫与代谢重点实验室,江苏                                徐州 221004
              1                                          2


             [摘    要] 磷酸果糖激酶肌型(phosphofructokinase,muscle type,PFKM)是糖酵解途径关键限速酶,其表达与活性受到缺氧诱
              导因子⁃1α(hypoxia⁃inducible factor⁃1 alpha,HIF⁃1α)、髓细胞瘤癌基因(myelocytomatosis oncogene,Myc)、磷脂酰肌醇⁃3⁃激酶/蛋
              白激酶 B(phosphoinositide 3⁃kinase/protein kinase B,PI3K/AKT)及腺苷 5′⁃单磷酸活化蛋白激酶(adenosine 5′⁃monophosphate⁃
              activated protein kinase,AMPK)等信号通路的调控。近年来研究发现,PFKM通过经典糖酵解途径和非经典分子功能影响巨噬
              细胞功能。微环境中的机械力、葡萄糖、柠檬酸等理化因素可通过调节PFKM四聚体⁃二聚体的构象平衡,推进PFKM经典与非
              经典功能之间的转换。目前研究多聚集于PFKM的经典糖酵解功能,其非经典功能及其中分子机制仍亟待阐明。文章综述了
              PFKM在巨噬细胞中的经典与非经典功能、上游调控信号及其在感染性疾病与肿瘤中的作用,旨在为靶向PFKM的免疫代谢治
              疗策略提供新的理论依据与参考。
             [关键词] 磷酸果糖激酶肌型;糖酵解;巨噬细胞;感染;肿瘤
             [中图分类号] R730.21                   [文献标志码] A                      [文章编号] 1007⁃4368(2026)04⁃598⁃09
              doi:10.7655/NYDXBNSN251438



              Research progress on the regulation of macrophage function by PFKM through classical
              and non⁃classical pathways

                       1,2
                                   1,2
              YAO Chen ,YANG Jing ,PAN Yuchen    1,2*
                                                                                          2
              1 Department of Pathogen Biology and Immunology,School of Basic Medical Sciences,Jiangsu Provincial Key
              Laboratory of Immunology and Metabolism,Xuzhou Medical University,Xuzhou 221004,China

             [Abstract] Phosphofructokinase,muscle type(PFKM)is a key rate⁃limiting enzyme in the glycolytic pathway,and its expression and
              activity are regulated by multiple signaling pathways,including hypoxia⁃inducible factor⁃1 alpha(HIF⁃1α),myelocytomatosis oncogene
             (Myc),phosphoinositide 3⁃kinase/protein kinase B(PI3K/AKT),and adenosine 5′⁃monophosphate(AMP)⁃activated protein kinase
             (AMPK). Recent studies have demonstrated that PFKM reprograms macrophage functions through both the canonical glycolytic
              pathway and“non⁃canonical”functions. Physicochemical factors in the microenvironment,including mechanical forces,glucose,and
              citrate,can shift the equilibrium between the tetrameric and dimeric conformations of PFKM,thereby facilitating the switch between its
              classical and non⁃classical functions. While current research has largely focused on the classical glycolytic role of PFKM,its non⁃
              canonical functions and the underlying molecular mechanisms remain to be fully elucidated. This review summarizes the classical and
              non⁃canonical roles of PFKM in macrophages,its upstream regulatory signals,and its implications in infectious diseases and cancer,

              aiming to provide a theoretical foundation and insights for PFKM⁃targeted immunometabolic therapeutic strategies.
             [Key words] phosphofructokinase muscle type;glycolysis;macrophages;infection;tumor
                                                                            [J Nanjing Med Univ,2026,46(04):598⁃606]






                  磷酸果糖激酶肌型(phosphofructokinase,muscle           type,PFKM)是催化糖酵解途径限速步骤的关键酶
                                                                磷酸果糖激酶⁃1(phosphofructokinase⁃1,PFK⁃1)的一
             [基金项目] 国家自然科学基金(82502134)
                                                                种同工酶,由位于染色体12q13.11的PFKM基因编码,
              ∗
               通信作者(Corresponding author),E⁃mail:panyuchen@xzhmu.
                                                                                  [1]
              edu.cn(ORCID:0000⁃0001⁃9260⁃4562)                 其分子量约为85 kDa 。已知糖酵解途径中共有3个
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