Thrombopoietic effects of CCAAT/enhancer-binding protein ß on the early-stage differentiation of megakaryocytes.
Arch Biochem Biophys
; 703: 108846, 2021 05 30.
Article
em En
| MEDLINE
| ID: mdl-33744198
ABSTRACT
CCAAT/enhancer-binding protein ß (C/EBPß) is a transcription factor that is involved in adipocytic and monocytic differentiation. However, the physiological role of C/EBPß in megakaryocytes (MKs) is not clear. In this study, we investigated the effects of C/EBPß on the early-stage differentiation of MKs, and explored the potential mechanisms of action. We established a cytosine arabinoside-induced thrombocytopenia mouse model using C57BL/6 mice. In the thrombocytopenia mice, the platelet count was found to be decreased, and the mRNA and protein expression levels of C/EBPß in MKs were also reduced. Furthermore, the maturation of Dami (MKs cell line) cells was induced by phorbol 12-myristate 13-acetate. When C/EBPß was silenced in Dami cells by transfection using C/EBPß-small interfering RNA, the expression of MKs-specific markers CD41 and CD62P, was dramatically decreased, resulting in morphological changes and differentiation retardation in low ploidy, which were evaluated using flow cytometry, real-time polymerase chain reaction, western blot, and confocal microscopy. The mitogen activated protein kinase-extracellular signal-regulated kinase signaling pathway was found to be required for the differentiation of MKs; knockdown of C/EBPß in MEK/ERK1/2 pathway attenuated MKs differentiation. Overexpression of C/EBPß in MEK/ERK1/2 pathway inhibited by U0126 did not promote MKs differentiation. To the best of our knowledge, C/EBPß plays an important role in MKs differentiation and polyploidy cell cycle control. Taken together, C/EBPß may have thrombopoietic effects in the differentiation of MKs, and may assist in the development of treatments for various disorders.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Megacariócitos
/
Diferenciação Celular
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Proteína beta Intensificadora de Ligação a CCAAT
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Trombopoese
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Arch Biochem Biophys
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China