血小板生成减少是免疫性血小板减少症（ITP）关键发病机制，目前认为巨核细胞成熟障碍是血小板生成减少的核心环节，阐明血小板生成减少机制是该领域的重大科学问题；申请者在前期研究中发现，ITP患者骨髓血管微环境巨核细胞PPF功能障碍可能是ITP发病的关键机制；以ITP巨核细胞表达S1P为切入点，初步阐明其介导巨核细胞迁移、成熟过程，进一步分析SphK2/SFK和S1PR1对巨核细胞Rac-GTPase的调控作用，并深入研究ITP巨核细胞PAK/Stathmin信号传导通路及其关键分子靶点；探讨其对ITP巨核细胞微管形成的影响，以及揭示巨核细胞PPF功能障碍分子机制，国内外尚未见相关报道。本课题进一步拓展和补充ITP发病机制理论，可能为临床治疗ITP提供新思路及新靶点。

Decreased platelet production, of which megakaryocyte maturation disorder is currently believed to be the core link, contributes critically to the pathogenesis of immune thrombocytopenia (ITP). To elucidate the mechanism of decreased platelet production is a major scientific issue in this field.; in previous studies, we found that PPF dysfunction of megakaryocytes in ITP patients may be a vital component in the development of this disease. Taking the expression of S1P in ITP megakaryocytes as a cut-in point, we clarify its mediation of megakaryocyte migration and maturation, further analyze the regulation of Sphk2/SFK and S1PR on megakaryocyte Rac-GTPase. Moreover, we explore the PAK/Stathmin signal transduction pathway in ITP megakaryocytes, as well as its pivotal molecular targets. In addition, we investigate the impact of such pathway on microtubules formation in ITP megakaryocytes, and molecular mechanism of PFs dysfunction in them, which has not been reported at home and abroad. This research further expands and supplements the pathogenesis theory of ITP, which may provide new ideas and targets for clinical treatment.