Serotonin Enhances Megakaryopoiesis and Proplatelet Formation via p-Erk1/2 and F-Actin Reorganization
Serotonin Enhances Megakaryopoiesis and Proplatelet Formation via p-Erk1/2 and F-Actin Reorganization
复制标题
血清素通过 p-Erk1/2 和 F-肌动蛋白重组增强巨核细胞生成和前血小板形成
DOI：
10.1002/stem.1777
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发表时间：
2014-11-01
期刊：
影响因子：
5.2
通讯作者：
Yang, Mo
中科院分区：
文献类型：
--
作者：
Ye, Jie Yu;Liang, En Yu;Yang, Mo
我们以前的研究表明，血清素（5-羟色胺; 5-HT）是造血干/祖细胞的生长因子。在本研究中，我们提出了一个可能的机制：5-HT可能通过Erk 1/2途径和细胞骨架重组促进巨核细胞和前血小板的形成。在此，5-HT 2BR首次在巨核细胞中被鉴定。5-HT还通过激活5-HT 2BR和Akt通路促进巨核细胞增殖，减少细胞凋亡。5-HT 2BR抑制剂酮色林可降低这种作用。进一步证实了5-HT对骨髓巨噬细胞前血小板形成的影响：5-HT治疗组较对照组有更多的带前血小板的巨噬细胞。为了确定5-HT是否对MK的细胞骨架重组有影响，以及这些影响是否可以被酮色林或Erk 1/2抑制剂PD 98059降低，用F-肌动蛋白特异性结合剂罗丹明-鬼笔环肽对MK进行染色。对照组的聚合肌动蛋白水平低于5-HT组，并分布在整个细胞质中，偶尔聚集。我们的数据表明，Erk 1/2在5-HT处理的MK中被激活。这项研究表明，5-HT对血小板形成具有强有力的作用，这种作用可能是通过5 HT（2B）R介导的，随后激活p-Erk 1/2，随后进行F-肌动蛋白重组和前血小板形成。我们还表明，褪黑激素，5-HT的代谢产物，发挥保护作用的MK和血小板的恢复在照射小鼠模型。本研究提示5-HT通过5-HT（2B）R、p-Erk 1/2和F-actin重组在血小板形成中起重要作用。
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-HT2BR was first identified in megakaryocytic cells. 5-HT also promoted the megakaryocytes (MKs) proliferation and reduced the cell apoptosis via the activation of 5-HT2BR and Akt pathway. The effects were reduced by the 5-HT2BR 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.