Fibroblast growth factor-21 as a novel metabolic factor for regulating thrombotic homeostasis

Sci Rep. 2022 Jan 10;12(1):400. doi: 10.1038/s41598-021-00906-2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Coagulation / drug effects*
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Cell Line
  • Cytokines / metabolism
  • Disease Models, Animal
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Factor VII / genetics
  • Factor VII / metabolism
  • Fibrinolysis / drug effects
  • Fibrinolytic Agents / pharmacology*
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Fibroblast Growth Factors / pharmacology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / metabolism
  • Plasminogen Activator Inhibitor 1 / genetics
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Platelet Activation / drug effects
  • Rabbits
  • Signal Transduction
  • Smad2 Protein / metabolism
  • Thrombosis / blood
  • Thrombosis / genetics
  • Thrombosis / prevention & control*
  • Tissue Plasminogen Activator / genetics
  • Tissue Plasminogen Activator / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • Cytokines
  • Fibrinolytic Agents
  • NF-kappa B
  • Plasminogen Activator Inhibitor 1
  • Smad2 Protein
  • Smad2 protein, mouse
  • Transforming Growth Factor beta
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Factor VII
  • Extracellular Signal-Regulated MAP Kinases
  • Tissue Plasminogen Activator