Platelet-derived growth factor B (PDGF-B) plays an essential role in hepatic fibrosis. Inhibition of the PDGF-B signaling in the 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. ELISA, 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 auto-antibodies. 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 activation of hepatic stellate cells in the fibrotic mouse livers. Collectively, 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.
- Received March 17, 2012.
- Revision received May 22, 2012.
- Accepted June 15, 2012.
- The American Society for Pharmacology and Experimental Therapeutics