Vaccination with Platelet-Derived Growth Factor B Kinoids Inhibits CCl4-Induced Hepatic Fibrosis in Mice

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 342; no. 3; pp. 835 - 842
• Main Authors: Hao, Zhi-Ming, Fan, Xiao-Bao, Li, Shuang, Lv, Yi-Fei, Su, Hou-Qiang, Jiang, Hui-Ping, Li, Hong-Hong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2012
• Subjects: Actins - immunology; Amino Acid Sequence; Animals; Antibodies, Neutralizing - immunology; Autoantibodies - immunology; Carbon Tetrachloride - antagonists & inhibitors; Carbon Tetrachloride - toxicity; Cell Growth Processes - immunology; Cells, Cultured; Desmin - immunology; Enzyme-Linked Immunosorbent Assay - methods; Epitopes, B-Lymphocyte - immunology; Hepatic Stellate Cells - immunology; Humans; Immunization - methods; Liver - immunology; Liver Cirrhosis - chemically induced; Liver Cirrhosis - immunology; Liver Cirrhosis - prevention & control; Male; Mice; Mice, Inbred BALB C; Molecular Sequence Data; NIH 3T3 Cells; Proliferating Cell Nuclear Antigen - immunology; Proto-Oncogene Proteins c-sis - immunology; Vaccination - methods; PBS; Ab; PCNA; EDC; KLH; SMA; MFB; PAGE; ECM; mAb; TGF; NC; PDGF; PDGFR; HSC; OVA; LI; BrdU; ELISA
• ISSN: 0022-3565; 1521-0103; 1521-0103
• DOI: 10.1124/jpet.112.194357

Platelet-derived growth factor B (PDGF-B) plays an essential role in hepatic fibrosis. Inhibition of the PDGF-B signaling in chronically injured livers might represent a potential therapeutic measure for hepatic fibrosis. In this study, we assessed the effects of vaccination against PDGF-B on CCl4-induced liver fibrosis in BALB/c mice. The PDGF-B kinoid immunogens were prepared by cross-linking two PDGF-B-derived B-cell epitope peptides [PDGF-B16-(23–38) and PDGF-B16-(72–83)] to ovalbumin and keyhole limpet hemocyanin, respectively. Enzyme-linked immunosorbent assay, Western blotting, and NIH3T3 cell proliferation assay verified that immunization with the PDGF-B kinoids elicited the production of high levels of neutralizing anti-PDGF-B autoantibodies. The vaccination markedly alleviated CCl4-induced hepatic fibrosis, as indicated by the lessened morphological alternations and reduced hydroxyproline contents in the mouse livers. Moreover, immunohistochemical staining for proliferating cell nuclear antigen, α-smooth muscle actin, and desmin demonstrated that neutralization of PDGF-B inhibited both the proliferation and the activation of hepatic stellate cells in the fibrotic mouse livers. Taken together, this study demonstrated that vaccination with PDGF-B kinoids significantly suppressed CCl4-induced hepatic fibrosis in mice. Our results suggest that vaccination against PDGF-B might be developed into an effective, convenient, and safe therapeutic measure for the treatment of hepatic fibrosis.