血小板生成素信号通路的分子机制及对多种细胞的作用

Molecular Mechanism of Thrombopoietin Signal Pathways and Its New Effects

血小板生成素(TPO)是调控巨核细胞增殖、分化和血小板生成的特异性生长因子,同时对早期造血也具有重要的调节作用。研究已经证明,TPO通过与其受体c-mpl结合并激活多种信号通路从而发挥其生物学作用。这些信号通路主要有Jak/STAT,PI3K/Akt,Ras/MAPK等。这些信号通路被激活后可以改变一系列下游信号分子的表达水平,例如β-链蛋白、缺氧诱导因子-1α(HIF-1α)、骨形态发生蛋白和同源异型框蛋白等。这些信号分子与TPO的生物学效应密切相关。近年来,TPO在体内其他组织和细胞,例如心肌细胞、神经元、血管内皮细胞、成骨细胞和卵巢等组织的作用也受到了关注。本文从TPO生物学作用的分子机制及其对多种细胞的作用进行综述。

Thrombopoietin （TPO） is a major cytokine for megakaryocytopoiesis and thrombopoiesis, and also plays an important role in the regulation of early hematopoiesis. TPO activates a number of signal pathways to exert its biological function by binding to its receptor （c-mpl）. Once these signal pathways （including Jak/STAT, PI3K/Akt, Ras/MAPK） are activated, the expression of the downstream signal molecules can be changed, which then induces biological effects. Recent researches have suggested the novel functions of TPO in many systems. The receptor of TPO （c-mpl） has been shown not only present in hematological cells, but also in many other cells and organs, such as neurons, heart muscle cells, vessel endothelial cells and so on. TPO exerts a protective effect on these cells through the interaction with c-mpl. This review discusses the molecular mechanism of TPO signal and the effect of TPO on multi- nonhematopoietic cells.