title: Serotonin enhances megakaryopoiesis and proplatelet formation via p-Erk1/2 and F-actin reorganization.
abstract: 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.
authors: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou Avenue, Guangdong, People's Republic of China.
authors: Jie Yu
authors: JY
authors: Ye
authors: En Yu
authors: EY
authors: Liang
authors: Yuan Shan
authors: YS
authors: Cheng
authors: Godfrey C F
authors: GC
authors: Chan
authors: Yue
authors: Y
authors: Ding
authors: Fanyi
authors: F
authors: Meng
authors: Margaret H L
authors: MH
authors: Ng
authors: Beng H
authors: BH
authors: Chong
authors: Qizhou
authors: Q
authors: Lian
authors: Mo
authors: M
authors: Yang
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*
chemical_list: D000199:Actins; D012701:Serotonin; D048052:Mitogen-Activated Protein Kinase 3
keywords: Megakaryopoiesis; Proplatelet; Serotonin; melatonin; p-Erk1/2