Daucosterol regulates JAK2-STAT3 signaling pathway to promote megakaryocyte differentiation

IF 2.1 4区 医学 Q3 HEMATOLOGY Blood Cells Molecules and Diseases Pub Date : 2024-05-16 DOI:10.1016/j.bcmd.2024.102858
Zhongkang Zhang, Guangbin Shang, Zhen Lu, Jia Hu, Huizhen Liu, Ting Lu, Xiaonan Lu
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Abstract

Immune thrombocytopenia (ITP) is an autoimmune disease caused by the loss of immune tolerance to platelet autoantigens, resulting in reduced platelet production and increased platelet destruction. Impaired megakaryocyte differentiation and maturation is a key factor in the pathogenesis and treatment of ITP. Sarcandra glabra, a plant of the Chloranthaceae family, is commonly used in clinical practice to treat ITP, and daucosterol (Dau) is one of its active ingredients. However, whether Dau can treat ITP and the key mechanism of its effect are still unclear. In this study, we found that Dau could effectively promote the differentiation and maturation of megakaryocytes and the formation of polyploidy in the megakaryocyte differentiation disorder model constructed by co-culturing Dami and HS-5 cells. In vivo experiments showed that Dau could not only increase the number of polyploidized megakaryocytes in the ITP rat model, but also promote the recovery of platelet count. In addition, through network pharmacology analysis, we speculated that the JAK2-STAT3 signaling pathway might be involved in the process of Dau promoting megakaryocyte differentiation. Western blot results showed that Dau inhibited the expression of P-JAK2 and P-STAT3. In summary, these results provide a basis for further studying the pharmacological mechanism of Dau in treating ITP.

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杜仲甾醇调节 JAK2-STAT3 信号通路,促进巨核细胞分化
免疫性血小板减少症(ITP)是一种自身免疫性疾病,由血小板自身抗原免疫耐受丧失引起,导致血小板生成减少和血小板破坏增加。巨核细胞分化和成熟受损是导致 ITP 发病和治疗的关键因素。沙苑子是一种绿茶科植物,临床上常用于治疗 ITP,而杜仲酚(Dau)是其活性成分之一。然而,Dau 是否能治疗 ITP 及其作用的关键机制仍不清楚。本研究发现,在达美和HS-5细胞共培养的巨核细胞分化障碍模型中,Dau能有效促进巨核细胞的分化和成熟以及多倍体的形成。体内实验表明,Dau不仅能增加ITP大鼠模型中多倍体化巨核细胞的数量,还能促进血小板数量的恢复。此外,通过网络药理学分析,我们推测JAK2-STAT3信号通路可能参与了Dau促进巨核细胞分化的过程。Western blot结果显示,Dau抑制了P-JAK2和P-STAT3的表达。总之,这些结果为进一步研究Dau治疗ITP的药理机制提供了依据。
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来源期刊
CiteScore
4.90
自引率
0.00%
发文量
42
审稿时长
14 days
期刊介绍: Blood Cells, Molecules & Diseases emphasizes not only blood cells, but also covers the molecular basis of hematologic disease and studies of the diseases themselves. This is an invaluable resource to all those interested in the study of hematology, cell biology, immunology, and human genetics.
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