Growth factor midkine : Biological significance, action mechanism, tissue repairing activity and relationship with diseases.

1.Midkine的三维结构经核磁共振测定，Midkine由2个结构域组成，每个结构域有3个antiitiparrel β折叠。具有生物活性的C-结构域的定点突变使我们能够鉴定神经突生长和纤溶酶原激活剂增强活性所需的氨基酸。2.中期因子具有中性粒细胞趋化活性，在类风湿关节炎患者的滑液中发现，表明其与炎症密切相关。中期因子促进中性粒细胞中Ca^2+的动员;通过使用信号转导的特异性抑制剂，酪氨酸激酶、P13激酶和G蛋白连接受体被认为参与了这一过程。3.产生缺乏中期因子基因的敲除小鼠。海马发育正常，但生后发育延迟。4.将中期因子mRNA注射到非洲爪蟾胚胎中，发现中期因子抑制中胚层诱导，促进头部神经元的发育。Smad 2下游的信号转导与中期因子信号通路相互作用。5.中期因子包被的珠子诱导肌肉细胞中乙酰胆碱受体的聚集。结合中期因子在突触中的表达，中期因子被认为是神经元分泌的促进突触发生的因子。6.缺失N端结构域的截短中期因子mRNA以肿瘤特异性的方式表达。在淋巴结转移灶中，截短型表达较强。中期因子的血清水平经常升高的癌症患者，特别是在那些与肺癌。

1.3D structure of midkine was determined NMR.Midkine consists of 2 domains, which have 3 anitipararel beta-sheets. Site-directed mutagenesis of C-domain, which has biological activity, enabled us to identify amino acids required for neurite outgrowth and plasminogen activator enhancing activity. 2.Midkine had neutrophil chemotactic activity, and was found in synovial fluid of rheumatoid arthritis patients, indicating its close correlation with inflammation. Midkine promotes Ca^<2+> mobilization in neutrophils ; by the use of specific inhibitors of signal transduction, tyrosine kinase, P13 kinase and a G-protein-linked receptor were proposed to be involved in the process. 3.Knockout mice lacking midkine gene were produced. They developed normally, but postnatal development of the hippocampus was delayd. 4.Injection of midkine mRNA into Xenopus embryos showed that midkine suppressed mesoderm induction and promoted development of head neurons. Signal transduction downstream from Smad 2 appeared to interact with midkine signaling pathway. 5.Midkine coated beads induced clustering of acetylcholine receptor in muscle cells. Together with midkine expression in synapses, midkine was concluded to be a factor which was secreted from neurons and promoted synaptogenesis. 6.Truncated midkine mRNA devoid of N terminal domain was expressed in a manner specific for tumor. The lymph node metastases showed strong expression of the truncated form. Serum levels of midkine was frequently elevated in cancer patients, especially in those with lung carcinomas.