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Thromb Haemost 2023; 123(02): 192-206
DOI: 10.1055/a-1947-7615
Cellular Haemostasis and Platelets

Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1B Inhibition Promotes Megakaryocyte Polyploidization and Platelet Production

Jiaxin Zhao‡   *
1   Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
,
Yanyan Xu‡   *
2   Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
,
Jiqiu Wang
2   Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
,
Junling Liu
3   Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
,
Ruiyan Zhang
1   Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
,
Xiaoxiang Yan
1   Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
› Author Affiliations Funding None.
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Abstract

Platelets are produced from mature megakaryocytes which undergo polyploidization and proplatelet formation. Cell-cycle regulation plays a crucial role in megakaryocyte terminal differentiation especially in polyploidization. Dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) controls cell-cycle progression in cancer cells. The objective of this study was to determine DYRK1B function in megakaryocyte maturation and platelet production. A DYRK1B knock-out mouse was generated with increased peripheral platelet count compared with the wild type mouse without affecting megakaryocyte numbers in bone marrow. Polyploidy and proplatelet formations were significantly enhanced when DYRK1B was depleted in vitro. DYRK1B inhibition promoted megakaryocyte maturation by simultaneously upregulating cyclin D1 and downregulating P27. Furthermore, there was platelet restoration in two mice disease models of transient thrombocytopenia. In summary, DYRK1B plays an important role in megakaryocyte maturation and platelet production by interacting with cyclin D1 and P27. DYRK1B inhibition has potential therapeutic value in transient thrombocytopenia treatment. [Graphic Abstract]

Keywords

platelet production - DYRK1B - cyclin D1 - P27

Data Sharing Statement

For original data, please contact cardexyanxx@hotmail.com.


* Contributed equally to this study.


Supplementary Material



Publication History

Received: 17 February 2022

Accepted: 17 September 2022

Accepted Manuscript online:
20 September 2022

Article published online:
28 December 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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