Melatonin (MT), endogenously secreted by the pineal gland, is closely related to multiple biological processes; however, its effect on thrombopoiesis is still not well illustrated. Here, we demonstrate that MT administration can elevate peripheral platelet levels. Analysis of different stages in thrombopoiesis reveals that MT has the capacity to promote the expansion of CD34+ and CD41+ cells, and accelerate proplatelet formation (PPF) and platelet production. Furthermore, in vivo experiments show that MT has a potential therapeutic effect on radiation-induced thrombocytopenia. The underlying mechanism suggests that both extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt signaling are involved in the processes of thrombopoiesis facilitated by MT. Interestingly, in addition to the direct regulation of Akt signaling by its upstream phosphoinositide 3-kinase (PI3K), ERK1/2 signaling is also regulated by PI3K via its effector, dual adaptor for phosphotyrosine and 3-phosphoinositides (DAPP1), in megakaryocytes after MT treatment. Moreover, the expression level of DAPP1 during megakaryocyte differentiation is closely related to the activation of ERK1/2 and Akt at different stages of thrombopoiesis. In conclusion, our data suggest that MT treatment can promote thrombopoiesis, which is modulated by the DAPP1-orchestrated activation of ERK1/2 and Akt signaling.

中文翻译：

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褪黑素通过磷酸酪氨酸和3-磷酸肌醇的双重衔接子协调的ERK1 / 2和Akt活化增强血小板生成。

松果体内源性分泌的褪黑激素（MT）与多种生物学过程密切相关；然而，其对血小板生成的作用仍未充分阐明。在这里，我们证明MT给药可以提高外周血血小板水平。对血小板生成过程不同阶段的分析表明，MT具有促进CD34 +和CD41 +细胞扩增，促进血小板原形成（PPF）和血小板生成的能力。此外，体内实验表明MT对放射线诱发的血小板减少症具有潜在的治疗作用。潜在的机制表明细胞外信号调节激酶1/2（ERK1 / 2）和Akt信号均参与MT促进的血小板生成过程。有趣的是 除MT处理后巨核细胞中的上游磷酸肌醇3激酶（PI3K）对Akt信号的直接调节外，PI3K还通过其效应子，磷酸酪氨酸和3-磷酸肌醇的双衔接子（DAPP1）对PI3K进行ERK1 / 2信号传导的调节。 。此外，在巨核细胞分化过程中，DAPP1的表达水平与血小板生成不同阶段的ERK1 / 2和Akt的激活密切相关。总之，我们的数据表明MT治疗可以促进血小板生成，这是由DAPP1调控的ERK1 / 2激活和Akt信号传导调节的。巨核细胞分化过程中DAPP1的表达水平与血小板生成不同阶段ERK1 / 2和Akt的激活密切相关。总之，我们的数据表明MT治疗可以促进血小板生成，这是由DAPP1调控的ERK1 / 2激活和Akt信号传导调节的。巨核细胞分化过程中DAPP1的表达水平与血小板生成不同阶段ERK1 / 2和Akt的激活密切相关。总之，我们的数据表明MT治疗可以促进血小板生成，这是由DAPP1调控的ERK1 / 2激活和Akt信号传导调节的。