title: Active immunization against transforming growth factor beta1 prevents hepatic fibrosis in a rat model of liver disease.
abstract: Transforming growth factor beta1 (TGF-β1) plays an important role in hepatic fibrogenesis. In this study, we documented the effects of active immunization against TGF-β1 on hepatic fibrosis in an animal model of chronic liver disease. BALB/c mice were immunized against 3 different peptides of TGF-β1 ligated into hepatitis B virus core protein (HBVc). Titers of TGF-β1 antibodies were documented by enzyme linked immunoassays and antibody activity by cell membrane receptor binding and proliferation assays. The most immunogenic recombinant HBVc + TGF-β1 peptide (HBVc + C) then served as a vaccine in Sprague-Dawley rats with dimethylnitrosamine-induced chronic liver disease. Hepatic fibrosis was documented by serum hyaluronic acid levels, liver histology, and reverse transcriptase polymerase chain reaction for hepatic collagen I (α1) and smooth muscle alpha actin mRNA expression. Relative to control rats vaccinated with HBVc alone, recombinant HBVc + C vaccinated animals had significantly lower serum hyaluronic acid levels, less histologic evidence of hepatic fibrosis, and reduced expression of collagen I (α1) and smooth muscle alpha actin mRNA in the liver. The results of this proof-of-concept study suggest that active immunization against TGF-β1 is a worthwhile strategy to pursue in efforts to prevent hepatic fibrosis associated with chronic liver disease.
authors.affiliation: a College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0T5, Canada.|b Section of Hepatology, Department of Internal Medicine, College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.affiliation: b Section of Hepatology, Department of Internal Medicine, College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
authors.forename: Gerald Y
authors.initials: GY
authors.lastname: Minuk
authors.affiliation: c Department of Pediatrics & Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
authors.forename: Zhikang
authors.initials: Z
authors.lastname: Peng
authors.affiliation: d The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang Province, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: d The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang Province, China.
authors.forename: Chenwei
authors.initials: C
authors.lastname: Pan
authors.affiliation: a College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0T5, Canada.|b Section of Hepatology, Department of Internal Medicine, College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Gong
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006515:Hepatitis B virus / Q000502:physiology; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000517:prevention & control* / Q000821:virology; D008807:Mice, Inbred BALB C; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000276:immunology*; D014611:Vaccination
chemical_list: D053773:Transforming Growth Factor beta1
keywords: facteur de croissance transformant bêta 1 (« transforming growth factor beta1 »); fibrose du foie; hepatitis B virus core protein; liver fibrosis; protéine nucléocapsidique du virus de l’hépatite B; protéine recombinante; recombinant protein; transforming growth factor beta1