Spleen Regulates Hematopoietic Stem/Progenitor Cell Functions Through Regulation of EGF in Cirrhotic Hypersplenism.
Spleen Regulates Hematopoietic Stem/Progenitor Cell Functions Through Regulation of EGF in Cirrhotic Hypersplenism.
复制标题
脾脏通过调节肝硬化脾功能亢进中的 EGF 来调节造血干/祖细胞功能。
DOI：
10.1007/s10620-018-5091-7
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发表时间：
2018
影响因子：
3.1
通讯作者：
Li Zongfang
中科院分区：
文献类型：
--
作者：
Wang Peijun;Li Zhenzhen;Ren Song;Li Jiangwei;Yang Jun;Kong Guangyao;Jiang An;Li Zongfang
背景造血功能异常是血小板增多性脾功能亢进（CH）患者常见的并发症和死亡原因，其严重的不良反应与出血、贫血、感染有关。然而，其内在机制尚不清楚。AimsWe旨在探讨脾脏对造血和造血干/祖细胞（HSPCs）在CH patients.MethodsEleven CH患者的造血干/祖细胞（HSPCs）功能的影响。流式细胞术分析造血变化。用集落形成试验和体外细胞培养检测HSPC功能。采用酶联免疫吸附试验（ELISA）检测各组脾组织中表皮生长因子（EGF）的含量。在体外实验中，CH患者血清可使HSPC功能失调，而脾切除患者血清可使失调的HSPC功能恢复。CH患者血清EGF浓度降低，脾切除后恢复正常。结论脾脏可通过调节EGF信号通路来调节CH患者HSPCs的功能。EGF可能是CH治疗的治疗靶点。
BackgroundHematopoietic abnormality is a common cause of cirrhotic hypersplenism (CH) complications and death; it causes serious adverse effects and is associated with bleeding, anemia, infection in CH patients. However, the underlying mechanism is unclear.AimsWe aimed to investigate the effects of the spleen on hematopoiesis and hematopoietic stem/progenitor cells (HSPCs) in CH patients.MethodsEleven CH patients were enrolled to assess the effects of the spleen on HSPC functions. Hematopoietic changes were examined by flow cytometry analysis. HSPC functions were detected with colony-forming assays and in vitro cell cultures. Enzyme-linked immunosorbent assay (ELISA) was used to test the concentration of epithelial growth factor (EGF).ResultsThe number of HSPCs was decreased in CH patients and was rescued after splenectomy. Serum from CH patients dysregulated HSPCs function, and serum from splenectomy patients restored the dysregulated HSPC function in vitro. The concentration of EGF was decreased in CH patients and was restored to normal level after splenectomy. EGF rescued the dysregulated HSPCs function in vitro.ConclusionsThe spleen can regulate the functions of HSPCs in CH patients by regulating EGF signaling. EGF may be a therapeutic target for CH treatment.