Platelet glycoprotein VI and C-type lectin-like receptor 2 deficiency accelerates wound healing by impairing vascular integrity in mice.
Animals
Biomarkers
Female
Fluorescent Antibody Technique
Immunohistochemistry
Lectins, C-Type
/ deficiency
Macrophages
/ immunology
Male
Membrane Glycoproteins
/ deficiency
Mice
Mice, Knockout
Neovascularization, Physiologic
/ genetics
Neutrophils
/ immunology
Platelet Membrane Glycoproteins
/ deficiency
Skin
/ metabolism
Wound Healing
/ genetics
Journal
Haematologica
ISSN: 1592-8721
Titre abrégé: Haematologica
Pays: Italy
ID NLM: 0417435
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
12
10
2018
accepted:
28
01
2019
pubmed:
9
2
2019
medline:
17
6
2020
entrez:
9
2
2019
Statut:
ppublish
Résumé
Platelets promote wound healing by forming a vascular plug and by secreting growth factors and cytokines. Glycoprotein (GP)VI and C-type lectin-like receptor (CLEC)-2 signal through a (hem)-immunoreceptor tyrosine-based activation motif, which induces platelet activation. GPVI and CLEC-2 support vascular integrity during inflammation in the skin through regulation of leukocyte migration and function, and by sealing sites of vascular damage. In this study, we investigated the role of impaired vascular integrity due to GPVI and/or CLEC-2 deficiency in wound repair using a full-thickness excisional skin wound model in mice. Transgenic mice deficient in both GPVI and CLEC-2 exhibited accelerated skin wound healing, despite a marked impairment in vascular integrity. The local and temporal bleeding in the skin led to greater plasma protein entry, including fibrinogen and clotting factors, was associated with increased fibrin generation, reduction in wound neutrophils and M1 macrophages, decreased level of tumor necrosis factor (TNF)-α, and enhanced angiogenesis at day 3 after injury. Accelerated wound healing was not due to developmental defects in CLEC-2 and GPVI double-deficient mice as similar results were observed in GPVI-deficient mice treated with a podoplanin-blocking antibody. The rate of wound healing was not altered in mice deficient in either GPVI or CLEC-2. Our results show that, contrary to defects in coagulation, bleeding following a loss of vascular integrity caused by platelet CLEC-2 and GPVI deficiency facilitates wound repair by increasing fibrin(ogen) deposition, reducing inflammation, and promoting angiogenesis.
Identifiants
pubmed: 30733265
pii: haematol.2018.208363
doi: 10.3324/haematol.2018.208363
pmc: PMC6669159
doi:
Substances chimiques
Biomarkers
0
CLEC2B protein, human
0
Lectins, C-Type
0
Membrane Glycoproteins
0
Platelet Membrane Glycoproteins
0
platelet membrane glycoprotein VI
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1648-1660Subventions
Organisme : British Heart Foundation
ID : RG/13/18/30563
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH03/003
Pays : United Kingdom
Informations de copyright
Copyright© 2019 Ferrata Storti Foundation.
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