Ptpn11激活突变骨髓细胞来源的外泌体在骨髓增殖性肿瘤中的作用  

The role of exosomes derived from Ptpn11 activating mutant bone marrow cells in myeloproliferative neoplasma

作　　者：吴梦月 谭振亚 阚晨 杨帆[1] 周园琴 龚良菊 孟祥越 郑红[1] Wu Mengyue;Tan Zhenya;Kan Chen(Dept of Pathophysiology, Anhui Medical University, Hefei 230032)

机构地区：[1]安徽医科大学病理生理学教研室,合肥230032

出　　处：《安徽医科大学学报》2021年第11期1679-1686,共8页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81670097、81870085);2019年高校拔尖人才项目(编号:gxbjZD07);安徽医科大学博士基金(编号:XJ2020019);安徽医科大学科研提升计划(编号2019xkjT004);安徽省高层次人才平台奖补资助。

摘　　要：目的研究Ptpn11^(E76K/+);Mx1-Cre^(+)激活突变骨髓细胞来源的外泌体在骨髓增殖性肿瘤(MPN)进程中发挥的作用。方法分离Ptpn11^(E76K/+);Mx1-Cre^(+)激活突变骨髓细胞来源的外泌体,与含有正常造血干细胞(HSCs)的LSK细胞进行体外培养,通过尾静脉将突变骨髓细胞来源的外泌体注射到野生C57BL小鼠体内,观察外泌体在体内外发挥的作用,最后通过细胞因子试剂盒检测突变骨髓细胞来源的外泌体发生的改变。结果突变骨髓细胞来源的外泌体会携带相关炎性因子,加速正常HSCs的髓系分化能力,导致正常小鼠发生MPN样的表型。使用炎性因子拮抗剂之后小鼠的MPN症状有所缓解,外泌体中相关炎性因子的表达也降低。结论Ptpn11^(E76K/+);Mx1-Cre^(+)激活突变骨髓细胞来源的外泌体携带炎性因子导致小鼠发生MPN样表型,外泌体及其携带的炎性因子都可以作为MPN治疗的潜在靶点。Objective To explore the role of Ptpn11^(E76K/+);Mx1-Cre^(+)activating mutant bone marrow-derived exosomes in the occurrence of myeloproliferative neoplasma(MPN).Methods Ptpn11^(E76K/+);Mx1-Cre^(+)activating mutant bone marrow-derived exosomes were co-cultured with normal hematopoietic stem cells in vitro,and at the same time,mutant exosomes were injected into normal mice through the tail vein to observe the effects of exosomes in vivo.The mouse cytokine array panel was used to detect the specific changes in the exosomes derived from the mutant bone marrow.Results Exosomes derived from mutant bone marrow could carry series of inflammatory factors,which accelerated the myeloid differentiation of normal hematopoietic stem cells,leading to the occurrence of MPN in normal mice.After inhibiting inflammatory factors,the symptoms of MPN in mice were relieved,and the expression of inflammatory factors in exosomes also decreased.Conclusion Ptpn11^(E76K/+);Mx1-Cre^(+)activating mutant bone marrow-derived exosomes can trigger MPN in mice via inflammatory factors.Both exosomes and the inflammatory factors they carry can be potential targets for MPN therapy.

关 键 词：Ptpn11 激活突变 骨髓增殖性肿瘤 外泌体 炎症因子 

分 类 号：R363.2[医药卫生—病理学]