Factor XIII-A: An Indispensable “Factor” in Haemostasis and Wound Healing

Fahad Saeed M Alshehri; Claire Whyte; Nicola Mutch

doi:10.3390/ijms22063055

Factor XIII-A: An Indispensable “Factor” in Haemostasis and Wound Healing

Fahad Saeed M Alshehri, Claire Whyte, Nicola Mutch^* (Corresponding Author)

^*Corresponding author for this work

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Abstract

Factor XIII (FXIII) is a transglutaminase enzyme that catalyses the formation of ε-(γ-glutamyl)lysyl isopeptide bonds into protein substrates. The plasma form, FXIIIA2B2, has an established function in haemostasis, with fibrin being its principal substrate. A deficiency in FXIII manifests as a severe bleeding diathesis emphasising its crucial role in this pathway. The FXIII-A gene (F13A1) is expressed in cells of bone marrow and mesenchymal lineage. The cellular form, a homodimer of the A subunits denoted FXIII-A, was perceived to remain intracellular, due to the lack of a classical signal peptide for its release. It is now apparent that FXIII-A can be externalised from cells, by an as yet unknown mechanism. Thus, three pools of FXIII-A exist within the circulation: plasma where it circulates in complex with the inhibitory FXIII-B subunits, and the cellular form encased within platelets and monocytes/macrophages. The abundance of this transglutaminase in different forms and locations in the vasculature reflect the complex and crucial roles of this enzyme in physiological processes. Herein, we examine the significance of these pools of FXIII-A in different settings and the evidence to date to support their function in haemostasis and wound healing

Original language	English
Article number	3055
Journal	International Journal of Molecular Sciences
Volume	22
Issue number	6
DOIs	https://doi.org/10.3390/ijms22063055
Publication status	Published - 17 Mar 2021

Bibliographical note

Author Contributions: F.S.M.A. wrote the manuscript; C.S.W. supervised the research and wrote the manuscript; N.J.M. supervised the research and wrote the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding: Fahad S.M. Alshehri is supported by Royal Embassy of Saudi Arabia Cultural Bureau (KFMCS74). Claire S. Whyte and Nicola J. Mutch were supported by the British Heart Foundation project grants (PG/15/82/31721 and PG/20/17/35050).

Acknowledgments: All figures were prepared with https://biorender.com/ (accessed on 16 March 2021).

Keywords

Factor XIII-A
transglutaminase
cross-linking
cellular FXIII-A
haemostasis
wound healing

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title = "Factor XIII-A: An Indispensable “Factor” in Haemostasis and Wound Healing",

abstract = "Factor XIII (FXIII) is a transglutaminase enzyme that catalyses the formation of ε-(γ-glutamyl)lysyl isopeptide bonds into protein substrates. The plasma form, FXIIIA2B2, has an established function in haemostasis, with fibrin being its principal substrate. A deficiency in FXIII manifests as a severe bleeding diathesis emphasising its crucial role in this pathway. The FXIII-A gene (F13A1) is expressed in cells of bone marrow and mesenchymal lineage. The cellular form, a homodimer of the A subunits denoted FXIII-A, was perceived to remain intracellular, due to the lack of a classical signal peptide for its release. It is now apparent that FXIII-A can be externalised from cells, by an as yet unknown mechanism. Thus, three pools of FXIII-A exist within the circulation: plasma where it circulates in complex with the inhibitory FXIII-B subunits, and the cellular form encased within platelets and monocytes/macrophages. The abundance of this transglutaminase in different forms and locations in the vasculature reflect the complex and crucial roles of this enzyme in physiological processes. Herein, we examine the significance of these pools of FXIII-A in different settings and the evidence to date to support their function in haemostasis and wound healing",

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AB - Factor XIII (FXIII) is a transglutaminase enzyme that catalyses the formation of ε-(γ-glutamyl)lysyl isopeptide bonds into protein substrates. The plasma form, FXIIIA2B2, has an established function in haemostasis, with fibrin being its principal substrate. A deficiency in FXIII manifests as a severe bleeding diathesis emphasising its crucial role in this pathway. The FXIII-A gene (F13A1) is expressed in cells of bone marrow and mesenchymal lineage. The cellular form, a homodimer of the A subunits denoted FXIII-A, was perceived to remain intracellular, due to the lack of a classical signal peptide for its release. It is now apparent that FXIII-A can be externalised from cells, by an as yet unknown mechanism. Thus, three pools of FXIII-A exist within the circulation: plasma where it circulates in complex with the inhibitory FXIII-B subunits, and the cellular form encased within platelets and monocytes/macrophages. The abundance of this transglutaminase in different forms and locations in the vasculature reflect the complex and crucial roles of this enzyme in physiological processes. Herein, we examine the significance of these pools of FXIII-A in different settings and the evidence to date to support their function in haemostasis and wound healing

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Factor XIII-A: An Indispensable “Factor” in Haemostasis and Wound Healing

Abstract

Bibliographical note

Keywords

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