The role of CREG1 in megakaryocyte maturation and thrombocytopoiesis

Song, HaiXu; Li, Jiayin; Peng, Chengfei; Liu, Dan; Mei, Zhu; Yang, Zheming; Tian, Xiaoxiang; Zhang, Xiaolin; Jing, Quanmin; Yan, Chenghui; Han, Yaling

doi:10.7150/ijbs.78660

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Int J Biol Sci 2023; 19(11):3614-3627. doi:10.7150/ijbs.78660 This issue Cite

Research Paper

The role of CREG1 in megakaryocyte maturation and thrombocytopoiesis

HaiXu Song^1#, Jiayin Li^1,2#, Chengfei Peng^1#, Dan Liu¹, Zhu Mei¹, Zheming Yang^1,2, Xiaoxiang Tian¹, Xiaolin Zhang¹, Quanmin Jing¹, Chenghui Yan^1✉, Yaling Han^1✉

1. National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China.
2. Northeastern University, Shenyang, China.
^#Co-first authors

Citation:

Song H, Li J, Peng C, Liu D, Mei Z, Yang Z, Tian X, Zhang X, Jing Q, Yan C, Han Y. The role of CREG1 in megakaryocyte maturation and thrombocytopoiesis. Int J Biol Sci 2023; 19(11):3614-3627. doi:10.7150/ijbs.78660. https://www.ijbs.com/v19p3614.htm

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Abstract

Abnormal megakaryocyte maturation and platelet production lead to platelet-related diseases and impact the dynamic balance between hemostasis and bleeding. Cellular repressor of E1A-stimulated gene 1 (CREG1) is a glycoprotein that promotes tissue differentiation. However, its role in megakaryocytes remains unclear. In this study, we found that CREG1 protein is expressed in platelets and megakaryocytes and was decreased in the platelets of patients with thrombocytopenia. A cytosine arabinoside-induced thrombocytopenia mouse model was established, and the mRNA and protein expression levels of CREG1 were found to be reduced in megakaryocytes. We established megakaryocyte/platelet conditional knockout (Creg1^pf4-cre) and transgenic mice (tg-Creg1). Compared to Creg1^fl/fl mice, Creg1^pf4-cre mice exhibited thrombocytopenia, which was mainly caused by inefficient bone marrow (BM) thrombocytopoiesis, but not by apoptosis of circulating platelets. Cultured Creg1^pf4-cre-megakaryocytes exhibited impairment of the actin cytoskeleton, with less filamentous actin, significantly fewer proplatelets, and lower ploidy. CREG1 directly interacts with MEK1/2 and promotes MEK1/2 phosphorylation. Thus, our study uncovered the role of CREG1 in the regulation of megakaryocyte maturation and thrombopoiesis, and it provides a possible theoretical basis for the prevention and treatment of thrombocytopenia.

Keywords: CREG1, megakaryocyte differentiation, thrombopoiesis, MEK-ERK1/2 pathway

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APA

Song, H., Li, J., Peng, C., Liu, D., Mei, Z., Yang, Z., Tian, X., Zhang, X., Jing, Q., Yan, C., Han, Y. (2023). The role of CREG1 in megakaryocyte maturation and thrombocytopoiesis. International Journal of Biological Sciences, 19(11), 3614-3627. https://doi.org/10.7150/ijbs.78660.

ACS

Song, H.; Li, J.; Peng, C.; Liu, D.; Mei, Z.; Yang, Z.; Tian, X.; Zhang, X.; Jing, Q.; Yan, C.; Han, Y. The role of CREG1 in megakaryocyte maturation and thrombocytopoiesis. Int. J. Biol. Sci. 2023, 19 (11), 3614-3627. DOI: 10.7150/ijbs.78660.

NLM

CSE

Song H, Li J, Peng C, Liu D, Mei Z, Yang Z, Tian X, Zhang X, Jing Q, Yan C, Han Y. 2023. The role of CREG1 in megakaryocyte maturation and thrombocytopoiesis. Int J Biol Sci. 19(11):3614-3627.

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