TRAF3 negatively regulates platelet activation and thrombosis

Rui Zhang, Guoying Zhang, Binggang Xiang, Xiaofeng Chen, Lijang Tang, Shaojun Shi, Yani Liu, Xun Ai, Ping Xie, Zhenyu Li

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily, binds to CD40, leading to many effects depending on target cell type. Platelets express CD40L and are a major source of soluble CD40L. CD40L has been shown to potentiate platelet activation and thrombus formation, involving both CD40-dependent and -independent mechanisms. A family of proteins called TNF receptor associated factors (TRAFs) plays key roles in mediating CD40L-CD40 signaling. Platelets express several TRAFs. It has been shown that TRAF2 plays a role in CD40L-mediated platelet activation. Here we show that platelet also express TRAF3, which plays a negative role in regulating platelet activation. Thrombin- or collagen-induced platelet aggregation and secretion are increased in TRAF3 knockout mice. The expression levels of collagen receptor GPVI and integrin αIIbβ3 in platelets were not affected by deletion of TRAF3, suggesting that increased platelet activation in the TRAF3 knockout mice was not due to increased expression platelet receptors. Time to formation of thrombi in a FeCl3-induced thrombosis model was significantly shortened in the TRAF3 knockout mice. However, mouse tail-bleeding times were not affected by deletion of TRAF3. Thus, TRAF3 plays a negative role in platelet activation and in thrombus formation in vivo.

Original languageEnglish (US)
Article number17112
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

TNF Receptor-Associated Factor 3
Platelet Activation
CD40 Ligand
Thrombosis
Blood Platelets
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Knockout Mice
TNF Receptor-Associated Factor 2
Bleeding Time
Platelet Aggregation
Integrins
Thrombin
Tail
Collagen
Tumor Necrosis Factor-alpha

All Science Journal Classification (ASJC) codes

  • General

Cite this

Zhang, R., Zhang, G., Xiang, B., Chen, X., Tang, L., Shi, S., ... Li, Z. (2017). TRAF3 negatively regulates platelet activation and thrombosis. Scientific reports, 7(1), [17112]. https://doi.org/10.1038/s41598-017-17189-1
Zhang, Rui ; Zhang, Guoying ; Xiang, Binggang ; Chen, Xiaofeng ; Tang, Lijang ; Shi, Shaojun ; Liu, Yani ; Ai, Xun ; Xie, Ping ; Li, Zhenyu. / TRAF3 negatively regulates platelet activation and thrombosis. In: Scientific reports. 2017 ; Vol. 7, No. 1.
@article{77cef95db7ec42b1bf132de8f9ae9888,
title = "TRAF3 negatively regulates platelet activation and thrombosis",
abstract = "CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily, binds to CD40, leading to many effects depending on target cell type. Platelets express CD40L and are a major source of soluble CD40L. CD40L has been shown to potentiate platelet activation and thrombus formation, involving both CD40-dependent and -independent mechanisms. A family of proteins called TNF receptor associated factors (TRAFs) plays key roles in mediating CD40L-CD40 signaling. Platelets express several TRAFs. It has been shown that TRAF2 plays a role in CD40L-mediated platelet activation. Here we show that platelet also express TRAF3, which plays a negative role in regulating platelet activation. Thrombin- or collagen-induced platelet aggregation and secretion are increased in TRAF3 knockout mice. The expression levels of collagen receptor GPVI and integrin αIIbβ3 in platelets were not affected by deletion of TRAF3, suggesting that increased platelet activation in the TRAF3 knockout mice was not due to increased expression platelet receptors. Time to formation of thrombi in a FeCl3-induced thrombosis model was significantly shortened in the TRAF3 knockout mice. However, mouse tail-bleeding times were not affected by deletion of TRAF3. Thus, TRAF3 plays a negative role in platelet activation and in thrombus formation in vivo.",
author = "Rui Zhang and Guoying Zhang and Binggang Xiang and Xiaofeng Chen and Lijang Tang and Shaojun Shi and Yani Liu and Xun Ai and Ping Xie and Zhenyu Li",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-17189-1",
language = "English (US)",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

Zhang, R, Zhang, G, Xiang, B, Chen, X, Tang, L, Shi, S, Liu, Y, Ai, X, Xie, P & Li, Z 2017, 'TRAF3 negatively regulates platelet activation and thrombosis', Scientific reports, vol. 7, no. 1, 17112. https://doi.org/10.1038/s41598-017-17189-1

TRAF3 negatively regulates platelet activation and thrombosis. / Zhang, Rui; Zhang, Guoying; Xiang, Binggang; Chen, Xiaofeng; Tang, Lijang; Shi, Shaojun; Liu, Yani; Ai, Xun; Xie, Ping; Li, Zhenyu.

In: Scientific reports, Vol. 7, No. 1, 17112, 01.12.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - TRAF3 negatively regulates platelet activation and thrombosis

AU - Zhang, Rui

AU - Zhang, Guoying

AU - Xiang, Binggang

AU - Chen, Xiaofeng

AU - Tang, Lijang

AU - Shi, Shaojun

AU - Liu, Yani

AU - Ai, Xun

AU - Xie, Ping

AU - Li, Zhenyu

PY - 2017/12/1

Y1 - 2017/12/1

N2 - CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily, binds to CD40, leading to many effects depending on target cell type. Platelets express CD40L and are a major source of soluble CD40L. CD40L has been shown to potentiate platelet activation and thrombus formation, involving both CD40-dependent and -independent mechanisms. A family of proteins called TNF receptor associated factors (TRAFs) plays key roles in mediating CD40L-CD40 signaling. Platelets express several TRAFs. It has been shown that TRAF2 plays a role in CD40L-mediated platelet activation. Here we show that platelet also express TRAF3, which plays a negative role in regulating platelet activation. Thrombin- or collagen-induced platelet aggregation and secretion are increased in TRAF3 knockout mice. The expression levels of collagen receptor GPVI and integrin αIIbβ3 in platelets were not affected by deletion of TRAF3, suggesting that increased platelet activation in the TRAF3 knockout mice was not due to increased expression platelet receptors. Time to formation of thrombi in a FeCl3-induced thrombosis model was significantly shortened in the TRAF3 knockout mice. However, mouse tail-bleeding times were not affected by deletion of TRAF3. Thus, TRAF3 plays a negative role in platelet activation and in thrombus formation in vivo.

AB - CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily, binds to CD40, leading to many effects depending on target cell type. Platelets express CD40L and are a major source of soluble CD40L. CD40L has been shown to potentiate platelet activation and thrombus formation, involving both CD40-dependent and -independent mechanisms. A family of proteins called TNF receptor associated factors (TRAFs) plays key roles in mediating CD40L-CD40 signaling. Platelets express several TRAFs. It has been shown that TRAF2 plays a role in CD40L-mediated platelet activation. Here we show that platelet also express TRAF3, which plays a negative role in regulating platelet activation. Thrombin- or collagen-induced platelet aggregation and secretion are increased in TRAF3 knockout mice. The expression levels of collagen receptor GPVI and integrin αIIbβ3 in platelets were not affected by deletion of TRAF3, suggesting that increased platelet activation in the TRAF3 knockout mice was not due to increased expression platelet receptors. Time to formation of thrombi in a FeCl3-induced thrombosis model was significantly shortened in the TRAF3 knockout mice. However, mouse tail-bleeding times were not affected by deletion of TRAF3. Thus, TRAF3 plays a negative role in platelet activation and in thrombus formation in vivo.

UR - http://www.scopus.com/inward/record.url?scp=85038096981&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85038096981&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-17189-1

DO - 10.1038/s41598-017-17189-1

M3 - Article

AN - SCOPUS:85038096981

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 17112

ER -

Zhang R, Zhang G, Xiang B, Chen X, Tang L, Shi S et al. TRAF3 negatively regulates platelet activation and thrombosis. Scientific reports. 2017 Dec 1;7(1). 17112. https://doi.org/10.1038/s41598-017-17189-1