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https://hdl.handle.net/2440/27532
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dc.contributor.author | Lau, D. | - |
dc.contributor.author | Luxon, B. | - |
dc.contributor.author | Xiao, S. | - |
dc.contributor.author | Beard, M. | - |
dc.contributor.author | Lemon, S. | - |
dc.date.issued | 2005 | - |
dc.identifier.citation | Hepatology, 2005; 42(2):273-281 | - |
dc.identifier.issn | 0270-9139 | - |
dc.identifier.issn | 1527-3350 | - |
dc.identifier.uri | http://hdl.handle.net/2440/27532 | - |
dc.description.abstract | To gain insight into pathogenic mechanisms underlying fibrosis in hepatitis C virus (HCV)-mediated liver injury, we compared intrahepatic gene expression profiles in HCV-infected patients at different stages of fibrosis and alpha-smooth muscle actin (alpha-SMA) staining patterns. We studied 21 liver biopsy specimens: 5 had no fibrosis (Ludwig-Batts stage 0); 10 had early portal or periportal fibrosis (stages 1 and 2); and 6, advanced fibrosis (stages 3 and 4). None of the patients had hepatocellular carcinoma. Transcriptional profiles were determined by high-density oligonucleotide microarrays. ANOVA identified 157 genes for which transcript abundance was associated with fibrosis stage. These defined three distinct hierarchical clusters of patients. Patients with predominantly stage 0 fibrosis had increased abundance of mRNAs linked to glycolipid metabolism. PDGF, a potent stellate cell mitogen, was also increased. Transcripts with increased abundance in stages 1 and 2 fibrosis were associated with oxidative stress, apoptosis, inflammation, proliferation, and matrix degradation, whereas transcripts increased in stages 3 and 4 were associated with fibrogenesis and cellular proliferation. Cells staining for alpha-SMA were detectable at all stages but infrequent in advanced fibrosis without active inflammation. A high frequency of such cells was associated with mRNAs linked to glycolipid metabolism. In conclusion, the presence of alpha-SMA-positive HSCs and expression of PDGF in stage 0 fibrosis suggests that stellate cells are activated early in HCV-mediated injury, possibly in response to oxidative stress resulting from inflammation and lipid metabolism. Increased abundance of transcripts linked to cellular proliferation in advanced fibrosis is consistent with a predisposition to cancer. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index/html). | - |
dc.description.statementofresponsibility | Daryl T.-Y. Lau, Bruce A. Luxon, Shu-Yuan Xiao, Michael R. Beard, and Stanley M. Lemon | - |
dc.language.iso | en | - |
dc.publisher | John Wiley & Sons Inc | - |
dc.source.uri | http://dx.doi.org/10.1002/hep.20767 | - |
dc.subject | Liver | - |
dc.subject | Humans | - |
dc.subject | Hepatitis C | - |
dc.subject | Liver Cirrhosis | - |
dc.subject | Actins | - |
dc.subject | Oligonucleotide Array Sequence Analysis | - |
dc.subject | Immunohistochemistry | - |
dc.subject | Gene Expression Profiling | - |
dc.subject | Adult | - |
dc.subject | Middle Aged | - |
dc.subject | Female | - |
dc.subject | Male | - |
dc.title | Intrahepatic gene expression profiles and alpha-smooth muscle actin patterns in hepatitis C virus induced fibrosis | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1002/hep.20767 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Beard, M. [0000-0002-4106-1016] | - |
Appears in Collections: | Aurora harvest 2 Molecular and Biomedical Science publications |
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