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Shear Stress Accumulation Enhances von Willebrand Factor-Induced Platelet P-Selectin Translocation in a PI3K/Akt Pathway-Dependent Manner

Platelet adhesion and activation through the interaction of von Willebrand factor (VWF) with platelet glycoprotein (GP) Ibα are the early key events in hemostasis and thrombosis especially under high blood shear stress. P-selectin translocation from α granule to the cell surface is a typical platele...

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Autores principales: Fang, Jinhua, Sun, Xiaoxi, Liu, Silu, Yang, Pu, Lin, Jiangguo, Feng, Jingjing, Cruz, Miguel A., Dong, Jing-fei, Fang, Ying, Wu, Jianhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204100/
https://www.ncbi.nlm.nih.gov/pubmed/34141704
http://dx.doi.org/10.3389/fcell.2021.642108
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author Fang, Jinhua
Sun, Xiaoxi
Liu, Silu
Yang, Pu
Lin, Jiangguo
Feng, Jingjing
Cruz, Miguel A.
Dong, Jing-fei
Fang, Ying
Wu, Jianhua
author_facet Fang, Jinhua
Sun, Xiaoxi
Liu, Silu
Yang, Pu
Lin, Jiangguo
Feng, Jingjing
Cruz, Miguel A.
Dong, Jing-fei
Fang, Ying
Wu, Jianhua
author_sort Fang, Jinhua
collection PubMed
description Platelet adhesion and activation through the interaction of von Willebrand factor (VWF) with platelet glycoprotein (GP) Ibα are the early key events in hemostasis and thrombosis especially under high blood shear stress. P-selectin translocation from α granule to the cell surface is a typical platelet function phenotype, which makes the platelet-induced inflammatory response of flowing leukocytes possible and can be induced by either chemical agonists (thrombin, ADP, etc.) or high blood shear stress, but regulations of VWF mutation and blood shear stress on VWF-induced P-selectin translocation remain unclear. With flow cytometry, parallel plate flow chamber, and immunofluorescence staining techniques, we examined the P-selectin translocation of platelets on immobilized wild-type (WT) VWF-A1 domain and its two mutants, the gain-of-function (GOF) mutant R1308L and the loss-of-function (LOF) mutant G1324S, respectively. The results showed that the VWF-A1-induced platelet P-selectin translocation was triggered, accelerated, and enhanced by fluid shear stress and could be correlated with shear stress accumulation (SSA, the product of fluid shear stress and mechanical stimulus time), and the PI3K/Akt axis was involved in the platelet P-selectin translocation. The force-triggered P-selectin translocation occurred quickly on partial platelet surface first and then extended gradually to the whole platelet surface as SSA increased. The P-selectin translocation process would be promoted by the GOF mutation (R1308L) but slowed down by the LOF mutation (G1324S). These findings demonstrated a force-enhanced regulation mechanism for the VWF-induced platelet P-selectin translocation through the PI3K/Akt pathway and provided a novel insight into the mechano-chemical regulation mechanism for the key events, such as platelet activation and functional phenotype change in hemostasis and thrombosis.
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spelling pubmed-82041002021-06-16 Shear Stress Accumulation Enhances von Willebrand Factor-Induced Platelet P-Selectin Translocation in a PI3K/Akt Pathway-Dependent Manner Fang, Jinhua Sun, Xiaoxi Liu, Silu Yang, Pu Lin, Jiangguo Feng, Jingjing Cruz, Miguel A. Dong, Jing-fei Fang, Ying Wu, Jianhua Front Cell Dev Biol Cell and Developmental Biology Platelet adhesion and activation through the interaction of von Willebrand factor (VWF) with platelet glycoprotein (GP) Ibα are the early key events in hemostasis and thrombosis especially under high blood shear stress. P-selectin translocation from α granule to the cell surface is a typical platelet function phenotype, which makes the platelet-induced inflammatory response of flowing leukocytes possible and can be induced by either chemical agonists (thrombin, ADP, etc.) or high blood shear stress, but regulations of VWF mutation and blood shear stress on VWF-induced P-selectin translocation remain unclear. With flow cytometry, parallel plate flow chamber, and immunofluorescence staining techniques, we examined the P-selectin translocation of platelets on immobilized wild-type (WT) VWF-A1 domain and its two mutants, the gain-of-function (GOF) mutant R1308L and the loss-of-function (LOF) mutant G1324S, respectively. The results showed that the VWF-A1-induced platelet P-selectin translocation was triggered, accelerated, and enhanced by fluid shear stress and could be correlated with shear stress accumulation (SSA, the product of fluid shear stress and mechanical stimulus time), and the PI3K/Akt axis was involved in the platelet P-selectin translocation. The force-triggered P-selectin translocation occurred quickly on partial platelet surface first and then extended gradually to the whole platelet surface as SSA increased. The P-selectin translocation process would be promoted by the GOF mutation (R1308L) but slowed down by the LOF mutation (G1324S). These findings demonstrated a force-enhanced regulation mechanism for the VWF-induced platelet P-selectin translocation through the PI3K/Akt pathway and provided a novel insight into the mechano-chemical regulation mechanism for the key events, such as platelet activation and functional phenotype change in hemostasis and thrombosis. Frontiers Media S.A. 2021-06-01 /pmc/articles/PMC8204100/ /pubmed/34141704 http://dx.doi.org/10.3389/fcell.2021.642108 Text en Copyright © 2021 Fang, Sun, Liu, Yang, Lin, Feng, Cruz, Dong, Fang and Wu. 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 Cell and Developmental Biology
Fang, Jinhua
Sun, Xiaoxi
Liu, Silu
Yang, Pu
Lin, Jiangguo
Feng, Jingjing
Cruz, Miguel A.
Dong, Jing-fei
Fang, Ying
Wu, Jianhua
Shear Stress Accumulation Enhances von Willebrand Factor-Induced Platelet P-Selectin Translocation in a PI3K/Akt Pathway-Dependent Manner
title Shear Stress Accumulation Enhances von Willebrand Factor-Induced Platelet P-Selectin Translocation in a PI3K/Akt Pathway-Dependent Manner
title_full Shear Stress Accumulation Enhances von Willebrand Factor-Induced Platelet P-Selectin Translocation in a PI3K/Akt Pathway-Dependent Manner
title_fullStr Shear Stress Accumulation Enhances von Willebrand Factor-Induced Platelet P-Selectin Translocation in a PI3K/Akt Pathway-Dependent Manner
title_full_unstemmed Shear Stress Accumulation Enhances von Willebrand Factor-Induced Platelet P-Selectin Translocation in a PI3K/Akt Pathway-Dependent Manner
title_short Shear Stress Accumulation Enhances von Willebrand Factor-Induced Platelet P-Selectin Translocation in a PI3K/Akt Pathway-Dependent Manner
title_sort shear stress accumulation enhances von willebrand factor-induced platelet p-selectin translocation in a pi3k/akt pathway-dependent manner
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204100/
https://www.ncbi.nlm.nih.gov/pubmed/34141704
http://dx.doi.org/10.3389/fcell.2021.642108
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