Document Detail


Newcastle disease virus represses the activation of human hepatic stellate cells and reverses the development of hepatic fibrosis in mice.
MedLine Citation:
PMID:  19192169     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: Activated hepatic stellate cells (HSCs) are the crucial factor responsible for liver fibrosis and involved in development of hepatocellular carcinoma (HCC) by interaction with tumour cells. Newcastle disease virus (NDV) has the oncolytic characteristics of intrinsically selective replication in neoplasia cells and transformed cells. But, NDV replication in HSCs and effects on hepatic fibrosis have not been reported.
METHODS: We detected the effect of conditioned medium (CM) from human HCC cells on the activation of human HSC line, LX-2 by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and reverse transcriptase-polymerase chain reaction (RT-PCR). The replication of NDV was evaluated in LX-2 cells and primary-cultured mouse HSCs by flow cytometry or by a fluorescence microscope. Indices for hepatic fibrosis were determined in HSCs and a hepatic fibrosis mouse model by gelatin zymography, RT-PCR, Western blot and Sirius red staining after NDV infection. Colocalization of NDV virions and alpha-smooth muscle actin (alpha-SMA) were detected by double immunofluorescence staining. Detection of apoptosis was carried out in liver tissues of NDV-treated mice by the TdT-mediated dUTP nick-end labelling assay.
RESULTS: Tumour-CM and transforming growth factor-beta1 (TGF-beta1) could promote the proliferation and activation of LX-2 cells, indicated by the enhanced expression of alpha-SMA, collagen I, tissue inhibitor of metalloproteinase (TIMP)-1 and TGF-beta1. Activated HSCs facilitated the replication of NDV, thereby repressing the secretion of MMP, the expression of these indices for hepatic fibrosis and the expression of alpha-SMA and collagen fibrils in hepatic fibrosis of the mouse induced by carbon tetrachloride.
CONCLUSIONS: HCC cells promote the activation of HSCs and NDV attenuates the activation and represses the hepatic fibrosis by selective replication in activated HSCs.
Authors:
Ya-Lin Li; Jiao Wu; Ding Wei; Da-Wei Zhang; Hao Feng; Zhi-Nan Chen; Huijie Bian
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-28
Journal Detail:
Title:  Liver international : official journal of the International Association for the Study of the Liver     Volume:  29     ISSN:  1478-3231     ISO Abbreviation:  Liver Int.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-27     Completed Date:  2009-06-25     Revised Date:  2011-07-15    
Medline Journal Info:
Nlm Unique ID:  101160857     Medline TA:  Liver Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  593-602     Citation Subset:  IM    
Affiliation:
State Key Laboratory of Cancer Biology, Cell Engineering Research Centre and Department of Cell Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, China.
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MeSH Terms
Descriptor/Qualifier:
Actins / genetics,  metabolism
Animals
Apoptosis / drug effects
Biological Markers / metabolism
Carcinoma, Hepatocellular / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Collagen Type I / genetics,  metabolism
Culture Media, Conditioned / pharmacology
Cytopathogenic Effect, Viral
Gene Expression Regulation
Hepatic Stellate Cells / drug effects,  metabolism*,  virology
Humans
Liver / drug effects,  metabolism*,  pathology,  virology
Liver Cirrhosis, Experimental / prevention & control*,  virology
Liver Neoplasms / metabolism
Mice
Newcastle disease virus / physiology*
Tetrazolium Salts / metabolism
Thiazoles / metabolism
Tissue Inhibitor of Metalloproteinase-1
Transforming Growth Factor beta1 / pharmacology
Virus Replication
Chemical
Reg. No./Substance:
0/ACTA2 protein, human; 0/Actins; 0/Biological Markers; 0/Collagen Type I; 0/Culture Media, Conditioned; 0/Tetrazolium Salts; 0/Thiazoles; 0/Tissue Inhibitor of Metalloproteinase-1; 0/Transforming Growth Factor beta1; 298-93-1/thiazolyl blue

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