5-HT Promotes Proliferation and Inhibits Apoptosis of Megakarycytes through 5-HT2BR.
10.19746/j.cnki.issn.1009-2137.2025.01.011
- Author:
Hui-Min KONG
1
;
Yu-Rong CEN
2
;
Mo YANG
2
;
Qiang PENG
3
;
Jin-Qi HUANG
2
Author Information
1. Department of Blood Transfusion, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, Guangdong Province, China.
2. Department of Hematology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong Province, China.
3. Emergency Department, Shenzhen Luohu Hospital Group Luohu People's Hospital, Shenzhen 518000, Guangdong Province, China.
- Publication Type:Journal Article
- Keywords:
5-HT;
Meg-01 cells;
5-HT2BR;
proliferation;
apoptosis
- MeSH:
Apoptosis/drug effects*;
Cell Proliferation/drug effects*;
Megakaryocytes/metabolism*;
Serotonin/pharmacology*;
Humans;
Receptor, Serotonin, 5-HT2B/metabolism*;
Caspase 3/metabolism*;
Cell Differentiation
- From:
Journal of Experimental Hematology
2025;33(1):75-81
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of 5-hydroxytryptamine (5-HT) on the proliferation, apoptosis and colony-forming unit-megakaryocyte (CFU-MK) of Meg-01 cells and its possible mechanisms.
METHODS:The uptake and metabolism of 5-HT in Meg-01 cells were analysed by reverse-phase high-performance liquid chromatography (RP-HPLC) with electrochemical detection. The expression of 5-HT2B receptor (5-HT2BR) in megakaryocytes was detected by immunofluorescence staining. The cell proliferation and viability were measured by MTT and Trypan blue staining after Meg-01 cells were single-cultured or co-cultured with different concentrations of 5-HT/5-HT2BR inhibitor Ketanserin for 48 h. Meg-01 cells were incubated with 5-HT/ Ketanserin for 72 h, then the flow cytometry was used to detect early apoptosis of the cells and the activity of caspase-3. Using CFU-MK assay to investigate the effect of 5-HT on the differentiation of megakaryocytes.
RESULTS:5-HT could be uptaken by Meg-01 cells, and metabolized into 5-hydroxyindoleacetic acid (5-HIAA). The expression of 5-HT2BR on megakaryocytes could be detected after immunofluorescence staining. 5-HT could promote the proliferation of Meg-01 cells at a dose-dependent manner (r =0.82), with the most significant effect observed at a concentration of 200 nmol/L (P < 0.001). Trypan blue staining also indicated that 200 nmol/L 5-HT had the most significant effect on the viability of Meg-01 cells (P < 0.05). The proliferation of Meg-01 cells treated with 5-HT was increased compared with the untreated control (P < 0.001), while the combination of 5-HT with ketanserin downregulated this effect. 5-HT significantly reduced the early apoptosis rate (P < 0.001) and caspase-3 activity (P < 0.05) of Meg-01 cells, while addition of ketanserin significantly increased the early apoptosis rate of Meg-01 cells (P < 0.001) and caspase-3 activity also increased to some extent. 5-HT promoted the formation of CFU-MK in bone marrow cells in a dose-dependent manner (r =0.89). The addition of ketanserin reduced the promoting effect of 5-HT on CFU-MK formation (P < 0.01).
CONCLUSION:There may be monoamine oxidase present in megakaryocytes, which can metabolize and decompose 5-HT into 5-HIAA. 5-HT may promote the proliferation and differentiation of megakaryocytes through 5-HT2BR. Besides, 5-HT can also reduce the apoptosis of megakaryocytes, and its anti-apoptotic effect may be mediated by 5-HT2BR and caspase-3 pathways.
