Collagen-binding vascular endothelial growth factor attenuates CCl4-induced liver fibrosis in mice.
Mol Med Rep
; 14(5): 4680-4686, 2016 Nov.
Article
em En
| MEDLINE
| ID: mdl-27748931
ABSTRACT
Vascular endothelial growth factor (VEGF) serves an important role in promoting angiogenesis and tissue regeneration. However, the lack of an effective delivery system that can target this growth factor to the injured site reduces its therapeutic efficacy. Therefore, in the current study, collagenbinding VEGF was constructed by fusing a collagenbinding domain (CBD) to the Nterminal of native VEGF. The CBDVEGF can specifically bind to collagen which is the major component of the extracellular matrix in fibrotic liver. The antifibrotic effects of this novel material were investigated by the carbon tetrachloride (CCl4)induced liver fibrotic mouse model. Mice were injected with CCl4 intraperitoneally to induce liver fibrosis. CBDVEGF was injected directly into the liver tissue of mice. The liver tissues were stained with hematoxylin and eosin for general observation or with Masson's trichrome staining for detection of collagen deposition. The hepatic stellate cell activation, blood vessel formation and hepatocyte proliferation were measured by immunohistochemical staining for αsmooth muscle actin, CD31 and Ki67 in the liver tissue. The fluorescent TUNEL assay was performed to evaluate the hepatocyte apoptosis. The present study identified that the CBDVEGF injection could significantly promote vascularization of the liver tissue of fibrotic mice and attenuate liver fibrosis. Furthermore, hepatocyte apoptosis and hepatic stellate cell activation were attenuated by CBDVEGF treatment. CBDVEGF treatment could additionally promote hepatocyte regeneration in the liver tissue of fibrotic mice. Thus, it was suggested that CBDVEGF may be used as a novel therapeutic intervention for liver fibrosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tetracloreto de Carbono
/
Colágeno
/
Fator A de Crescimento do Endotélio Vascular
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Cirrose Hepática Experimental
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2016
Tipo de documento:
Article