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J Hepatol. 2007 Apr;46(4):664-73. Epub 2006 Nov 27.

Expression of large tenascin-C splice variants by hepatic stellate cells/myofibroblasts in chronic hepatitis C.

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  • 1Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Mie, Japan.

Abstract

BACKGROUND/AIMS:

Earlier studies have suggested involvement of tenascin-C (TN-C) in liver fibrosis. Here, we examined expression of TN-C variants and types of alternatively spliced fibronectin-type III (FNIII) repeats in chronic hepatitis.

METHODS:

Using three monoclonal antibodies against TN-C variants, immunohistochemical staining was performed and the correlation with histological parameters of chronic hepatitis C was examined. The cellular source was also determined and variant expression and their types were tested using isolated rat hepatic stellate cells (HSCs), liver myofibroblasts, and/or LI90 cells.

RESULTS:

Large variants were not expressed in normal liver, but were up-regulated in chronic hepatitis, especially at sites of interface hepatitis and confluent necrosis, showing stronger correlations between staining intensity and these than with other parameters or fibrosis. TN-C deposition was closely correlated with increase in the number of alpha-smooth muscle actin-positive cells, i.e. activated HSCs/myofibroblasts, and in situ hybridization showed TN-C mRNA signals in the cells. Activated HSCs and myofibroblasts in culture highly expressed large variants of TN-C. In LI90 cells, sequencing of large variants revealed that the FNIII repeats D and A1/A4, followed by B, were preferentially included.

CONCLUSIONS:

TN-C and its variants are produced by HSCs/myofibroblasts, suggesting important roles in liver fibrogenesis.

PMID:
17188391
[PubMed - indexed for MEDLINE]
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