Abstract

CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor that is involved in adipocytic and monocytic differentiation. However, the physiological role of C/EBPβ in megakaryocytes (MKs) is not clear. In this study, we investigated the effects of C/EBPβ 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/EBPβ in MKs were also reduced. Furthermore, the maturation of Dami (MKs cell line) cells was induced by phorbol 12-myristate 13-acetate. When C/EBPβ was silenced in Dami cells by transfection using C/EBPβ-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/EBPβ in MEK/ERK1/2 pathway attenuated MKs differentiation. Overexpression of C/EBPβ in MEK/ERK1/2 pathway inhibited by U0126 did not promote MKs differentiation. To the best of our knowledge, C/EBPβ plays an important role in MKs differentiation and polyploidy cell cycle control. Taken together, C/EBPβ may have thrombopoietic effects in the differentiation of MKs, and may assist in the development of treatments for various disorders.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call