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Thromb Haemost
DOI: 10.1055/a-2235-7485
Cellular Haemostasis and Platelets

Platelet-Derived TGF-β1 Promotes Deep Vein Thrombosis

Sixuan Zhang‡   *
1   Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
2   Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
3   Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China
,
Yingying Li‡   *
1   Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
2   Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
3   Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China
,
Jie Zhang‡   *
1   Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
2   Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
3   Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China
,
Yueyue Sun
1   Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
2   Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
3   Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China
,
Xiang Chu
1   Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
2   Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
3   Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China
,
Xiang Gui
1   Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
2   Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
3   Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China
,
Huan Tong
1   Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
2   Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
3   Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China
,
Yangyang Ding
1   Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
2   Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
3   Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China
,
Wen Ju
1   Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
2   Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
3   Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China
,
Mengdi Xu
1   Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
2   Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
3   Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China
,
Zhenyu Li
1   Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
2   Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
3   Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China
,
Lingyu Zeng   **
1   Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
2   Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
3   Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China
,
Kailin Xu   **
1   Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
2   Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
3   Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China
,
Jianlin Qiao   **
1   Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
2   Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
3   Key Laboratory of Bone Marrow Stem Cell, Xuzhou, China
› Author Affiliations Funding This work was supported by the National Natural Science Foundation of China (grant no. 82322005, 82261138554, 82170130, 81970124, and 81400082), the Natural Science Foundation of Jiangsu Province (grant no. BK20140219), the funding for the Distinguished Professorship Program of Jiangsu Province, the Shuangchuang Project of Jiangsu Province, the 333 projects of Jiangsu Province (BRA2017542), the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (18KJA320010), Jiangsu Province's Graduate Scientific Research Innovation Program (KYCX23-2930, KYCX22-2896 and KYCX21-2691), and the Youth Science and Technology Innovation Team of Xuzhou Medical University.
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Abstract

Background Transforming growth factor-β1 (TGF-β1) modulates multiple cellular functions during development and tissue homeostasis. A large amount of TGF-β1 is stored in platelet α-granules and released upon platelet activation. Whether platelet-derived TGF-β1 plays a role in venous thrombosis remains unclear. This study intends to assess the role of platelet-derived TGF-β1 in the development of venous thrombosis in mice.

Material and Methods TGF-β1flox/flox and platelet-specific TGF-β1−/− mice were utilized to assess platelet function in vitro, arterial thrombosis induced by FeCl3, tail bleeding time, prothrombin time (PT), activated partial thromboplastin time (APTT), and deep vein thrombosis induced through ligation of the inferior vena cava (IVC). The IVC sample was collected to measure accumulation of neutrophils, monocytes, and the formation of neutrophil extracellular traps (NETs) by immunofluorescence staining.

Results TGF-β1 deficiency in platelets did not affect the number of circulating platelets, platelet aggregation, adenosine triphosphate release, and integrin αIIbβ3 activation. Meanwhile, TGF-β1 deficiency did not alter the arterial thrombus formation, hemostasis, and coagulation time (PT and APTT), but significantly impaired venous thrombus formation, inhibited the recruitment and accumulation of neutrophils and monocytes in thrombi, as well as reduced formation of NETs and platelet-neutrophil complex. In addition, adoptive transfer of TGF-β1flox/flox platelets to TGF-β1−/− mice rescued the impaired venous thrombus formation, recruitment of leukocytes and monocytes, as well as the NETs formation.

Conclusion In conclusion, platelet-derived TGF-β1 positively modulates venous thrombus formation in mice, indicating that targeting TGF-β1 might be a novel approach for treating venous thrombosis without increasing the risk of bleeding.

Keywords

platelets - TGF-β1 - venous thrombosis - neutrophils extracellular traps - bleeding

Authors' Contribution

S.Z., Y.L., and J.Z. performed research, analyzed data, and wrote the manuscript. X.C., Y.S., X.G., H.T., Y.D., W.J., M.X., and Z.L. performed research and analyzed data. L.Z., K.X., and J.Q. conceived and designed the study and wrote the manuscript.


* These authors contributed equally to this study.


** These authors shares equal senior authorship.


Supplementary Material



Publication History

Received: 06 July 2023

Accepted: 17 December 2023

Accepted Manuscript online:
27 December 2023

Article published online:
15 January 2024

© 2024. Thieme. All rights reserved.

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Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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