摘要
巨噬细胞迁移抑制因子(macrophage migration inhibitory factor,MIF)是一类多效性的前炎症细胞因子,能够促进其他多种前炎症因子的分泌或表达。其基因在大多数哺乳动物基因组中具有90%的同源性。MIF启动子区含有能够与多种转录因子结合的DNA结合位点,同时含有与其表达水平相关的多态性位点。MIF发挥其生物学功能,一方面可以通过非受体介导的内吞作用,实现MIF与c-Jun激活结构域结合蛋白-1(JAB1)的相互作用;另一方面,受体依赖型的MIF能够激活包括PI3K/AKT、MAPK和G蛋白偶联受体相关的信号传导途径等。此外,MIF还能够通过直接或间接方式调节肿瘤抑制基因p53的功能。MIF已经被证实参与调解炎症、肿瘤生成和纤维化等生物学过程。从MIF表达、相关受体、涉及的信号通路与生物学过程等方面,对其分子功能的研究进展进行了总结,并对MIF相关的分子机理进行了综述,旨在为MIF相关疾病的诊断和治疗提供线索。
Macrophage migration inhibitory factor( MIF) is one of the pleiotropic pro-inflammatory cytokines that promotes the secretion or expression of many other pro-inflammatory cytokines. At gene level it has 90% homology in the most of the mammalian genomes. The promoter region of MIF contains DNA-binding sites which could bind to a variety of transcription factors,as well as polymorphic sites associated with the expression level of MIF. MIF exerts its biological function by receptordependent or independent ways. In the receptor-independent approach,MIF is in taken by non-receptor-mediated endocytosis and interacts with c-Jun activation domain binding protein-1( JAB1). During the receptor-dependent pathway,MIF interacts with its receptors and further activates signaling pathways including PI3 K/AKT,MAPK and G protein-coupled receptors related signal cascades. Moreover,MIF can also directly or indirectly regulate the function of tumor suppressor gene p53. Due to its strong biological function,MIF has been confirmed to participate in the mediation of biological processes such as inflammation,tumorigenesis and fibrosis. This article summarized the research progress in molecular function of MIF expression,related receptors,involved signal pathways and biological processes,and reviewed the related molecular mechanisms,with the hope of providing clues for the diagnose and treatment of MIF-related diseases.
引文
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