Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou Avenue, Guangdong, People's Republic of China.
Stem Cells. 2014 Nov;32(11):2973-82. doi: 10.1002/stem.1777.
Our previous studies have shown that serotonin (5-hydroxytryptamine; 5-HT) is a growth factor for hematopoietic stem/progenitor cells. In this study, we proposed a possible mechanism: 5-HT may enhance megakaryopoiesis and proplatelet formation via Erk1/2 pathway and cytoskeleton reorganization. Here, 5-HT(2B)R was first identified in megakaryocytic cells. 5-HT also promoted the megakaryocytes (MKs) proliferation and reduced the cell apoptosis via the activation of 5-HT(2B)R and Akt pathway. The effects were reduced by the 5-HT2B R inhibitor ketanserin. The effect of 5-HT on proplatelet formation in bone marrow MKs were further confirmed: the 5-HT treated group had more proplatelet bearing MKs compared with the control group. To determine whether 5-HT has effects on cytoskeleton reorganization of MKs, and whether these effects could be reduced by ketanserin or Erk1/2 inhibitor PD98059, MKs were stained with the F-actin specific binder rhodamine-phalloidin. The polymerized actin level was lower in the control group than the 5-HT group and was distributed throughout the cytoplasm with occasional aggregations. Our data demonstrated that Erk1/2 was activated in MKs treated with 5-HT. This study suggests that 5-HT has a potent effect on platelet formation and this effect is likely mediated via 5HT(2B)R with subsequent activation of p-Erk1/2 and consequent F-actin reorganization and proplatelet formation. We also demonstrated that melatonin, the metabolite of 5-HT, exerts a protective effect on MK and platelet recovery in the irradiated mouse model. This study suggested that 5-HT plays an important role in platelet formation via 5HT(2B)R, p-Erk1/2, and F-actin reorganization.
我们之前的研究表明，5-羟色胺（5-HT）是造血干细胞/祖细胞的生长因子。在这项研究中，我们提出了一种可能的机制：5-HT 可能通过 Erk1/2 途径和细胞骨架重排增强巨核细胞生成和前血小板形成。在这里，首次在巨核细胞中鉴定出 5-HT2B 受体。5-HT 还通过激活 5-HT2B 受体和 Akt 途径促进巨核细胞（MKs）增殖并减少细胞凋亡。这种作用被 5-HT2B 受体抑制剂酮色林所减弱。5-HT 对骨髓 MKs 前血小板形成的影响进一步得到证实：与对照组相比，5-HT 处理组具有更多的前血小板携带 MKs。为了确定 5-HT 是否对 MKs 的细胞骨架重排有影响，以及这些影响是否可以被酮色林或 Erk1/2 抑制剂 PD98059 减弱，用 F-肌动蛋白特异性结合物罗丹明鬼笔环肽对 MKs 进行染色。与 5-HT 组相比，对照组的聚合肌动蛋白水平较低，分布在整个细胞质中，偶尔有聚集。我们的数据表明，5-HT 处理的 MKs 中 Erk1/2 被激活。这项研究表明，5-HT 对血小板形成有很强的作用，这种作用可能是通过 5-HT2B 受体介导的，随后激活 p-Erk1/2，继而导致 F-肌动蛋白重排和前血小板形成。我们还表明，5-HT 的代谢产物褪黑素对辐照小鼠模型中的 MK 和血小板恢复具有保护作用。这项研究表明，5-HT 通过 5-HT2B 受体、p-Erk1/2 和 F-肌动蛋白重排在血小板形成中发挥重要作用。
