Vaccination with platelet-derived growth factor B kinoids inhibits CCl₄-induced hepatic fibrosis in mice.
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.
Department of Gastroenterology, the First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, 277 Yantaxilu, Xi'an 710061, China. haozhm@yahoo.com.cn
Zhi-Ming
ZM
Hao
Xiao-Bao
XB
Fan
Shuang
S
Li
Yi-Fei
YF
Lv
Hou-Qiang
HQ
Su
Hui-Ping
HP
Jiang
Hong-Hong
HH
Li
D000199:Actins / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D002251:Carbon Tetrachloride / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D048708:Cell Growth Processes / Q000276:immunology; D002478:Cells, Cultured; D003893:Desmin / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D055166:Hepatic Stellate Cells / Q000276:immunology; D006801:Humans; D007114:Immunization / Q000379:methods; D008099:Liver / Q000276:immunology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D018809:Proliferating Cell Nuclear Antigen / Q000276:immunology; D020574:Proto-Oncogene Proteins c-sis / Q000276:immunology*; D014611:Vaccination / Q000379:methods
D000199:Actins; D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D003893:Desmin; D018985:Epitopes, B-Lymphocyte; D018809:Proliferating Cell Nuclear Antigen; D020574:Proto-Oncogene Proteins c-sis; C544013:alpha-smooth muscle actin, mouse; D002251:Carbon Tetrachloride