Von Willebrand factor deficiency reduces liver fibrosis in mice

Toxicology and Applied Pharmacology
Nikita JoshiJames P Luyendyk

Abstract

Liver diseases are associated with complex changes in the hemostatic system and elevated levels of the platelet-adhesive protein Von Willebrand factor (VWF) are reported in patients with acute and chronic liver damage. Although elevated levels of VWF are associated with fibrosis in the general population, the role of VWF in acute and chronic liver injury has not been examined in depth in experimental settings. We tested the hypothesis that VWF deficiency inhibits experimental liver injury and fibrosis. Wild-type (WT) and VWF-deficient mice were challenged with carbon tetrachloride (CCl4) and the impact of VWF deficiency on acute liver injury and chronic liver fibrosis was determined. VWF deficiency did not significantly affect acute CCl4-induced hepatocellular necrosis in mice. Chronic CCl4 challenge, twice weekly for 6weeks, significantly increased hepatic stellate cell activation and collagen deposition in livers of WT mice. Interestingly, hepatic induction of several profibrogenic and stellate cell activation genes was attenuated in VWF-deficient mice. Moreover, birefringent sirius red staining (indicating type I and III collagens) and type I collagen immunofluorescence indicated a reduction in hepatic collagen deposition in...Continue Reading

Citations

Nov 28, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Georg P GyöriPatrick Starlinger
Nov 12, 2018·Journal of Thrombosis and Haemostasis : JTH·L G PooleJ P Luyendyk
Aug 17, 2018·European Journal of Gastroenterology & Hepatology·Nathalie I CaversaccioAnne Angelillo-Scherrer
Oct 1, 2020·Liver International : Official Journal of the International Association for the Study of the Liver·Giada PietrosiJordi Gracia-Sancho
Jul 21, 2020·Research and Practice in Thrombosis and Haemostasis·Lauren G PooleJames P Luyendyk
Apr 4, 2021·International Journal of Molecular Sciences·Marion MussbacherAlice Assinger
Mar 29, 2021·Journal of Thrombosis and Haemostasis : JTH·Dafna J GroeneveldJames P Luyendyk

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