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PD-L1 Regulates Platelet Activation and Thrombosis via Caspase-3/GSDME Pathway

Platelets play a central role in hemostasis and thrombosis, regulating the occurrence and development of thrombotic diseases, including ischemic stroke. Programmed death ligand 1 (PD-L1) has recently been detected in platelet, while the function of PD-L1 in platelets remain elusive. Our data reveal...

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Autores principales: Li, Yulong, Xin, Guang, Li, Shiyi, Dong, Yuman, Zhu, Yuda, Yu, Xiuxian, Wan, Chengyu, Li, Fan, Wei, Zeliang, Wang, Yilan, Zhang, Kun, Chen, Qingqiu, Niu, Hai, Huang, Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240427/
https://www.ncbi.nlm.nih.gov/pubmed/35784685
http://dx.doi.org/10.3389/fphar.2022.921414
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author Li, Yulong
Xin, Guang
Li, Shiyi
Dong, Yuman
Zhu, Yuda
Yu, Xiuxian
Wan, Chengyu
Li, Fan
Wei, Zeliang
Wang, Yilan
Zhang, Kun
Chen, Qingqiu
Niu, Hai
Huang, Wen
author_facet Li, Yulong
Xin, Guang
Li, Shiyi
Dong, Yuman
Zhu, Yuda
Yu, Xiuxian
Wan, Chengyu
Li, Fan
Wei, Zeliang
Wang, Yilan
Zhang, Kun
Chen, Qingqiu
Niu, Hai
Huang, Wen
author_sort Li, Yulong
collection PubMed
description Platelets play a central role in hemostasis and thrombosis, regulating the occurrence and development of thrombotic diseases, including ischemic stroke. Programmed death ligand 1 (PD-L1) has recently been detected in platelet, while the function of PD-L1 in platelets remain elusive. Our data reveal a novel mechanism for the role of PD-L1 on platelet activation and arterial thrombosis. PD-L1 knockout does not affect platelet morphology, count, and mean volume under homeostasis and without risk of bleeding, which inhibits platelet activation by suppressing outside-in-activation of integrin by downregulating the Caspase-3/GSDME pathway. Platelet adoptive transfer experiments demonstrate that PD-L1 knockout inhibits thrombosis. And the absence of PD-L1 improves ischemic stroke severity and increases mice survival. Immunohistochemical staining of the internal structure of the thrombus proves that PD-L1 enhances the seriousness of the thrombus by inhibiting platelet activation. This work reveals a regulatory role of PD-L1 on platelet activation and thrombosis while providing novel platelet intervention strategies to prevent thrombosis.
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spelling pubmed-92404272022-06-30 PD-L1 Regulates Platelet Activation and Thrombosis via Caspase-3/GSDME Pathway Li, Yulong Xin, Guang Li, Shiyi Dong, Yuman Zhu, Yuda Yu, Xiuxian Wan, Chengyu Li, Fan Wei, Zeliang Wang, Yilan Zhang, Kun Chen, Qingqiu Niu, Hai Huang, Wen Front Pharmacol Pharmacology Platelets play a central role in hemostasis and thrombosis, regulating the occurrence and development of thrombotic diseases, including ischemic stroke. Programmed death ligand 1 (PD-L1) has recently been detected in platelet, while the function of PD-L1 in platelets remain elusive. Our data reveal a novel mechanism for the role of PD-L1 on platelet activation and arterial thrombosis. PD-L1 knockout does not affect platelet morphology, count, and mean volume under homeostasis and without risk of bleeding, which inhibits platelet activation by suppressing outside-in-activation of integrin by downregulating the Caspase-3/GSDME pathway. Platelet adoptive transfer experiments demonstrate that PD-L1 knockout inhibits thrombosis. And the absence of PD-L1 improves ischemic stroke severity and increases mice survival. Immunohistochemical staining of the internal structure of the thrombus proves that PD-L1 enhances the seriousness of the thrombus by inhibiting platelet activation. This work reveals a regulatory role of PD-L1 on platelet activation and thrombosis while providing novel platelet intervention strategies to prevent thrombosis. Frontiers Media S.A. 2022-06-15 /pmc/articles/PMC9240427/ /pubmed/35784685 http://dx.doi.org/10.3389/fphar.2022.921414 Text en Copyright © 2022 Li, Xin, Li, Dong, Zhu, Yu, Wan, Li, Wei, Wang, Zhang, Chen, Niu and Huang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Li, Yulong
Xin, Guang
Li, Shiyi
Dong, Yuman
Zhu, Yuda
Yu, Xiuxian
Wan, Chengyu
Li, Fan
Wei, Zeliang
Wang, Yilan
Zhang, Kun
Chen, Qingqiu
Niu, Hai
Huang, Wen
PD-L1 Regulates Platelet Activation and Thrombosis via Caspase-3/GSDME Pathway
title PD-L1 Regulates Platelet Activation and Thrombosis via Caspase-3/GSDME Pathway
title_full PD-L1 Regulates Platelet Activation and Thrombosis via Caspase-3/GSDME Pathway
title_fullStr PD-L1 Regulates Platelet Activation and Thrombosis via Caspase-3/GSDME Pathway
title_full_unstemmed PD-L1 Regulates Platelet Activation and Thrombosis via Caspase-3/GSDME Pathway
title_short PD-L1 Regulates Platelet Activation and Thrombosis via Caspase-3/GSDME Pathway
title_sort pd-l1 regulates platelet activation and thrombosis via caspase-3/gsdme pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240427/
https://www.ncbi.nlm.nih.gov/pubmed/35784685
http://dx.doi.org/10.3389/fphar.2022.921414
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