Extracellular PDI in thrombosis and vascular injury.

Wang, J; Hogg, PJ; Xu, X; Fang, C

Extracellular PDI in thrombosis and vascular injury.

Wang, J Hogg, PJ Xu, X Fang, C

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Publisher:: Springer Nature
Publication Type:: Journal Article
Citation:: Thromb J, 2025, 23, (1), pp. 76
Issue Date:: 2025-07-28

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Field	Value	Language
dc.contributor.author	Wang, J
dc.contributor.author	Hogg, PJ
dc.contributor.author	Xu, X
dc.contributor.author	Fang, C
dc.date.accessioned	2025-08-11T04:09:02Z
dc.date.available	2025-07-21
dc.date.available	2025-08-11T04:09:02Z
dc.date.issued	2025-07-28
dc.identifier.citation	Thromb J, 2025, 23, (1), pp. 76
dc.identifier.issn	1477-9560
dc.identifier.issn	1477-9560
dc.identifier.uri	http://hdl.handle.net/10453/189373
dc.description.abstract	Protein disulfide isomerase (PDI) catalyzes the reduction, oxidation, and isomerization of disulfide bonds. Although initially discovered as an endoplasmic reticulum (ER)-residing protein, PDI has been demonstrated to play critical roles on cell surfaces and in the extracellular milieu under different pathophysiological settings. During thrombosis extracellular PDI regulates both platelet activation and coagulation, while during vascular injury PDI modulates proinflammatory neutrophil recruitment and the homeostasis of vascular cells. The identification of PDI substrates using mass spectrometry-based techniques such as mechanism-based kinetic trapping and differential cysteine alkylation has significantly advanced our understanding of the mechanisms whereby extracellular PDI regulates these pathophysiological processes. PDI may reduce or oxidize allosteric disulfide bonds and change the function of adhesive receptors, coagulation-related plasma proteins and signaling molecules that are important during thrombosis and vascular injury responses. The catalytic cysteines of PDI can also be post-translationally modified to enable PDI to transmit redox active species. This review aims to summarize the most recent advances about the roles of extracellular PDI in thrombosis and vascular injury and their mechanisms. With the discovery of novel PDI inhibitors, this body of knowledge will provide novel opportunities to develop strategies for the treatment of thrombotic and vascular diseases.
dc.format	Electronic
dc.language	eng
dc.publisher	Springer Nature
dc.relation.ispartof	Thromb J
dc.relation.isbasedon	10.1186/s12959-025-00765-1
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	Cardiovascular System & Hematology
dc.subject.classification	3201 Cardiovascular medicine and haematology
dc.subject.classification	3214 Pharmacology and pharmaceutical sciences
dc.title	Extracellular PDI in thrombosis and vascular injury.
dc.type	Journal Article
utslib.citation.volume	23
utslib.location.activity	England
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated	2025-08-11T04:09:00Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	23
utslib.citation.issue	1

Abstract:

Protein disulfide isomerase (PDI) catalyzes the reduction, oxidation, and isomerization of disulfide bonds. Although initially discovered as an endoplasmic reticulum (ER)-residing protein, PDI has been demonstrated to play critical roles on cell surfaces and in the extracellular milieu under different pathophysiological settings. During thrombosis extracellular PDI regulates both platelet activation and coagulation, while during vascular injury PDI modulates proinflammatory neutrophil recruitment and the homeostasis of vascular cells. The identification of PDI substrates using mass spectrometry-based techniques such as mechanism-based kinetic trapping and differential cysteine alkylation has significantly advanced our understanding of the mechanisms whereby extracellular PDI regulates these pathophysiological processes. PDI may reduce or oxidize allosteric disulfide bonds and change the function of adhesive receptors, coagulation-related plasma proteins and signaling molecules that are important during thrombosis and vascular injury responses. The catalytic cysteines of PDI can also be post-translationally modified to enable PDI to transmit redox active species. This review aims to summarize the most recent advances about the roles of extracellular PDI in thrombosis and vascular injury and their mechanisms. With the discovery of novel PDI inhibitors, this body of knowledge will provide novel opportunities to develop strategies for the treatment of thrombotic and vascular diseases.

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http://hdl.handle.net/10453/189373