Aberrant expression of Notch signaling molecules in patients with immune thrombocytopenic purpura
Aberrant expression of Notch signaling molecules in patients with immune thrombocytopenic purpura
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免疫性血小板减少性紫癜患者Notch信号分子的异常表达
DOI：
10.1007/s00277-009-0790-y
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发表时间：
2010-02-01
影响因子：
3.5
通讯作者：
Hou, Ming
中科院分区：
文献类型：
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作者：
Ma, Daoxin;Dai, Jianjian;Hou, Ming
为了研究Notch信号通路在免疫性血小板减少性紫癜（ITP）中的作用，我们测量了ITP患者中11种Notch通路分子的表达并评估了它们的临床相关性。实时逆转录聚合酶链式反应结果显示ITP中部分Notch分子表达异常。 ITP 患者中 Notch1 和 Notch3 表达升高，而 Notch2 表达降低。至于Notch配体，仅DLL1在ITP中被发现下调。 Notch 靶基因 Hes1 的表达也上调。与 mRNA 水平一致，Western blot 也发现 Notch1 和 Hes1 蛋白表达升高。免疫细胞化学显示，ITP组Notch1在细胞膜、细胞质和部分细胞核中高表达，而对照组在细胞膜中表达较弱，ITP组Hes1在细胞核中表达高于对照组。我们的研究结果表明，Notch 通路的异常表达谱可能与 ITP 有关，而阻断 Notch1 通路可能是一个有前途的治疗概念。
To investigate the role of Notch signaling pathway in immune thrombocytopenic purpura (ITP), we measured the expression of 11 Notch pathway molecules in ITP patients and evaluated their clinical relevance. Real-time reverse transcriptase polymerase chain reaction results showed there was aberrant expression of some Notch molecules in ITP. Notch1 and Notch3 expression elevated, while Notch2 decreased statistically in ITP patients. As for Notch ligands, only DLL1 was found downregulated in ITP. The expression of Notch target gene, Hes1, was also upregulated. In accordance with the mRNA level, Notch1 and Hes1 protein expression was also found elevated by Western blot. Immunocytochemistry showed that Notch1 expressed highly in the cytomembrane, cytoplasm, and part of cellular nucleus for ITP while weak in cytomembrane for controls, and Hes1 of ITP was found expressed higher in cellular nucleus than that of controls. Our findings suggest that the aberrant expression profile of Notch pathway may be involved in ITP, and blockage of Notch1 pathway is likely a promising therapeutic concept.