title: A virus-like particle-based connective tissue growth factor vaccine suppresses carbon tetrachloride-induced hepatic fibrosis in mice.
abstract: Connective tissue growth factor (CTGF) has been recognized as a central mediator and promising therapeutic target in hepatic fibrosis. In this study, we generated a novel virus-like particle (VLP) CTGF vaccine by inserting the 138-159 amino acid (aa) fragment of CTGF into the central c/e1 epitope of C-terminus truncated hepatitis B virus core antigen (HBc, aa 1-149) using a prokaryotic expression system. Immunization of BALB/c mice with the VLP vaccine efficiently elicited the production of anti-CTGF neutralizing antibodies. Vaccination with this CTGF vaccine significantly protected BALB/c mice from carbon tetrachloride (CCl4)-induced hepatic fibrosis, as indicated by decreased hepatic hydroxyproline content and lower fibrotic score. CCl4 intoxication-induced hepatic stellate cell activation was inhibited by the vaccination, as indicated by decreased α-smooth muscle actin expression and Smad2 phosphorylation. Vaccination against CTGF also attenuated the over-expression of some profibrogenic factors, such as CTGF, transforming growth factor-β1, platelet-derived growth factor-B and tissue inhibitor of metalloproteinase-1 in the fibrotic mouse livers, decreased hepatocyte apoptosis and accelerated hepatocyte proliferation in the fibrotic mouse livers. Our results clearly indicate that vaccination against CTGF inhibits fibrogenesis, alleviates hepatocyte apoptosis and facilitate hepatic regeneration. We suggest that the vaccine should be developed into an effective therapeutic measure for hepatic fibrosis.
authors: The First Affiliated Hospital of Xi'an Jiaotong University, Department of Gastroenterology, Xi'an, 710061, P.R. China.
authors: Shuang
authors: S
authors: Li
authors: Shaanxi Provincial People's Hospital and the Third Affiliated Hospital of Xi'an Jiaotong University, Department of Gastroenterology, Xi'an, 710068, P.R. China.
authors: Yi-Fei
authors: YF
authors: Lv
authors: The First Affiliated Hospital of Xi'an Jiaotong University, Department of Gastroenterology, Xi'an, 710061, P.R. China.
authors: Hou-Qiang
authors: HQ
authors: Su
authors: The First Affiliated Hospital of Xi'an Jiaotong University, Department of Gastroenterology, Xi'an, 710061, P.R. China.
authors: Qian-Nan
authors: QN
authors: Zhang
authors: School of Medicine, Xi'an Jiaotong University, Research Center of Reproductive Medicine, Xi'an, 710061, P.R. China.
authors: Li-Rong
authors: LR
authors: Wang
authors: The First Affiliated Hospital of Xi'an Jiaotong University, Department of Gastroenterology, Xi'an, 710061, P.R. China.|The First Affiliated Hospital of Xi'an Jiaotong University, Department of Rheumatology, Xi'an, 710061, P.R. China.
authors: Zhi-Ming
authors: ZM
authors: Hao
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014612:Vaccines / Q000276:immunology / Q000494:pharmacology*; D014771:Virion
chemical_list: C526318:CCN2 protein, mouse; D006512:Hepatitis B Core Antigens; D011993:Recombinant Fusion Proteins; D014612:Vaccines; D055513:Connective Tissue Growth Factor