Fibroblast growth factor-21 as a novel metabolic factor for regulating thrombotic homeostasis.
Animals
Blood Coagulation
/ drug effects
Blood Platelets
/ drug effects
Cell Line
Cytokines
/ metabolism
Disease Models, Animal
Extracellular Signal-Regulated MAP Kinases
/ metabolism
Factor VII
/ genetics
Fibrinolysis
/ drug effects
Fibrinolytic Agents
/ pharmacology
Fibroblast Growth Factors
/ genetics
Humans
Male
Mice, Inbred ICR
NF-kappa B
/ metabolism
Plasminogen Activator Inhibitor 1
/ genetics
Platelet Activation
/ drug effects
Rabbits
Signal Transduction
Smad2 Protein
/ metabolism
Thrombosis
/ blood
Tissue Plasminogen Activator
/ genetics
Transforming Growth Factor beta
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
10 01 2022
10 01 2022
Historique:
received:
28
09
2020
accepted:
12
10
2021
entrez:
11
1
2022
pubmed:
12
1
2022
medline:
23
2
2022
Statut:
epublish
Résumé
Fibroblast growth factor-21 (FGF-21) performs a wide range of biological functions in organisms. Here, we report for the first time that FGF-21 suppresses thrombus formation with no notable risk of bleeding. Prophylactic and therapeutic administration of FGF-21 significantly improved the degree of vascular stenosis and reduced the thrombus area, volume and burden. We determined the antithrombotic mechanism of FGF-21, demonstrating that FGF-21 exhibits an anticoagulant effect by inhibiting the expression and activity of factor VII (FVII). FGF-21 exerts an antiplatelet effect by inhibiting platelet activation. FGF-21 enhances fibrinolysis by promoting tissue plasminogen activator (tPA) expression and activation, while inhibiting plasminogen activator inhibitor 1 (PAI-1) expression and activation. We further found that FGF-21 mediated the expression and activation of tPA and PAI-1 by regulating the ERK1/2 and TGF-β/Smad2 pathways, respectively. In addition, we found that FGF-21 inhibits the expression of inflammatory factors in thrombosis by regulating the NF-κB pathway.
Identifiants
pubmed: 35013379
doi: 10.1038/s41598-021-00906-2
pii: 10.1038/s41598-021-00906-2
pmc: PMC8748457
doi:
Substances chimiques
Cytokines
0
Fibrinolytic Agents
0
NF-kappa B
0
Plasminogen Activator Inhibitor 1
0
Smad2 Protein
0
Smad2 protein, mouse
0
Transforming Growth Factor beta
0
fibroblast growth factor 21
0
Fibroblast Growth Factors
62031-54-3
Factor VII
9001-25-6
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Tissue Plasminogen Activator
EC 3.4.21.68
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
400Subventions
Organisme : Heilongjiang Province Fundamental Research Funds for Young Scholar
ID : 135409219
Organisme : Heilongjiang Province Fundamental Research Funds for Young Scholar
ID : 135409219
Informations de copyright
© 2022. The Author(s).
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