Lymphatic blood filling in CLEC-2-deficient mouse models.
Blood-lymphatic separation
CLEC-2
platelets
podoplanin
Journal
Platelets
ISSN: 1369-1635
Titre abrégé: Platelets
Pays: England
ID NLM: 9208117
Informations de publication
Date de publication:
03 Apr 2021
03 Apr 2021
Historique:
pubmed:
5
3
2020
medline:
8
10
2021
entrez:
5
3
2020
Statut:
ppublish
Résumé
C-type lectin-like receptor 2 (CLEC-2) is considered as a potential drug target in settings of wound healing, inflammation, and infection. A potential barrier to this is evidence that CLEC-2 and its ligand podoplanin play a critical role in preventing lymphatic vessel blood filling in mice throughout life. In this study, this aspect of CLEC-2/podoplanin function is investigated in more detail using new and established mouse models of CLEC-2 and podoplanin deficiency, and models of acute and chronic vascular remodeling. We report that CLEC-2 expression on platelets is not required to maintain a barrier between the blood and lymphatic systems in unchallenged mice, post-development. However, under certain conditions of chronic vascular remodeling, such as during tumorigenesis, deficiency in CLEC-2 can lead to lymphatic vessel blood filling. These data provide a new understanding of the function of CLEC-2 in adult mice and confirm the essential nature of CLEC-2-driven platelet activation in vascular developmental programs. This work expands our understanding of how lymphatic blood filling is prevented by CLEC-2-dependent platelet function and provides a context for the development of safe targeting strategies for CLEC-2 and podoplanin.
Identifiants
pubmed: 32129691
doi: 10.1080/09537104.2020.1734784
pmc: PMC8443399
mid: NIHMS1729675
doi:
Substances chimiques
CLEC-2 protein, mouse
0
Lectins, C-Type
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
352-367Subventions
Organisme : British Heart Foundation
ID : CH/03/003/15571
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : British Heart Foundation
ID : RG/13/18/30563
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/15/13/31673
Pays : United Kingdom
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