Abstract
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.
Footnotes
This study was supported by the National Foundation of Natural Sciences, China [Grants 30871144, 81070351].
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
ABBREVIATIONS:
- HSC
- hepatic stellate cell
- MFB
- myofibroblast
- ECM
- extracellular matrix
- TGF
- transforming growth factor
- PDGF
- platelet-derived growth factor
- PDGFR
- platelet-derived growth factor receptor
- Ab
- antibody
- mAb
- monoclonal antibody
- KLH
- keyhole limpet hemocyanin
- OVA
- ovalbumin
- PBS
- phosphate-buffered saline
- ELISA
- enzyme-linked immunosorbent assay
- NC
- normal control
- PAGE
- polyacrylamide gel electrophoresis
- SMA
- smooth muscle actin
- BrdU
- 5-bromo-2′-deoxyuridine
- PCNA
- proliferating cell nuclear antigen
- LI
- labeling index
- EDC
- 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride.
- Received March 17, 2012.
- Accepted June 15, 2012.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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