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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., (© 2022. The Author(s).)

Fibroblast growth factor 21 (FGF-21) is a secreted protein, which has anti-diabetic and lipocaic effects, but its ability to protect against hepatic fibrosis has not been studied. In this study, we investigated the ability of FGF-21 to attenuate dimethylnitrosamine (DMN)-induced hepatic fibrogenesis in mice and the mechanism of its action. Hepatic fibrosis was induced by injection of DMN, FGF-21 was administered to the mice once daily in association with DMN injection till the end of the experiment. Histopathological examination, tissue 4-hydroxyproline content and expressions of smooth muscle α-actin (α-SMA) and collagen I were measured to assess hepatic fibrosis. Ethanol/PDGF-BB-activated hepatic stellate cells (HSCs) were used to understand the mechanisms of FGF-21 inhibited hepatic fibrogenesis. Results showed that FGF-21 treatment attenuated hepatic fibrogenesis and was associated with a significant decrease in intrahepatic fibrogenesis, 4-hydroxyproline accumulation, α-SMA expression and collagen I deposition. FGF-21 treatment inhibited the activation of HSCs via down-regulating the expression of TGF-β, NF-κB nuclear translocation, phosphorylation levels of smad2/3 and IκBα. Besides, FGF-21 treatment caused activated HSC apoptosis with increasing expression of Caspase-3, and decreased the ratio of Bcl-2 to Bax. In conclusion, FGF-21 attenuates hepatic fibrogenesis and inhibits the activation of HSC warranting the use of FGF-21 as a potential therapeutic agent in the treatment of hepatic fibrosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: In this study, we explored whether treatment with FGF-21 could prevent diethylnitrosamine (DEN) induced hepatocarcinogenesis in mice., Methods & Results: Hepatoma was induced by injection of DEN every three days for 18 weeks. For the prophylactic experiment, mice were firstly injected with FGF-21 for 2 weeks, then FGF-21 was administered to the mice once daily in association with DEN injection till the end of the experiment. The hepatoma incidence of mice treated with FGF-21 was 13.3%, while the incidence of mice treated with saline was 61.5%. To understand the mechanisms, we compared the expression of βklotho (KLB) and oxidative stress level in the livers between the mice treated with FGF-21 and saline. We found that FGF-21 could suppress DEN-induced oxidative stress and up-regulate the expression of KLB in the livers. To confirm these results, we compared the expression of KLB in L02 cells stimulated with or without FGF-21. Besides, we established DEN-induced oxidative stress cell model to affirm the relationship between FGF-21 and DEN-induced oxidative stress in vitro. Results showed that FGF-21 increased the expression of KLB and diminished the DEN-induced oxidative stress in vitro in a dose dependent manner., Conclusion: Systemic administration of FGF-21 can prevent DEN-induced hepatocarcinogenesis via suppressing oxidative stress and increasing the expression of KLB.

Rheumatoid arthritis, a chronic degenerative autoimmune disease is hallmarked by tenacious inflammation of synovial membranes causing cartilage destruction and bone erosion. The search for effective therapies to mitigate its degenerative conditions remains partly elusive. Fibroblast growth factor 21 (FGF21) is known to modulate inflammation, playing a significant role in immune-mediated diseases such as rheumatoid arthritis. Here, we histopathologically evaluate the therapeutic efficacy of FGF21 in collagen-induced arthritis (CIA) mice. CIA mice were subcutaneously treated with FGF21 (3 mg/kg) for three consecutive weeks. Arthritic severity was scored followed by histopathological evaluation of the joints and immunohistochemistry using rabbit ant-cathepsin K, IL-10, MMP1, and 3 antibodies. Our data revealed that FGF21 significantly mitigated the severity of arthritis. Histopathologically, the articular structure was considerably enhanced by FGF21 through the reduction in the expression of cathepsin K and MMP3 whiles upregulating the expression of IL-10. Taken together, our findings suggest that FGF21 preserves the integrity of the articular structure thereby preventing cartilage and bone destruction in CIA mice. FGF21, therefore, has therapeutic prospects in the treatment of RA. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor-21 (FGF21) is a member of the family of fibroblast growth factors (FGFs). FGF21 (synthesized by many organs) has been studied extensively for its role in the regulation of energy homeostasis. FGF21 came into the spotlight after its beneficial metabolic effects in reducing blood glucose, and weight in obesity were identified. Since then, FGF21 has been extensively exploited for therapeutic purposes and clinical applications with significant achievements. Its therapeutic roles in diabetes, obesity, cardiovascular diseases, fibrosis, cancer and aging among others have been studied over the last decade with significant strides making it a promising candidate for the management of chronic diseases. Here we review the therapeutic prospects of FGF21 with emphasis on the management of chronic diseases, and breakthroughs in its shortfalls. The future of FGF21 as a therapeutic agent is auspicious and will help revolutionize the world of medicine. [ABSTRACT FROM AUTHOR]