Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Hepatol. 2007 Nov;47(5):699-710. Epub 2007 Jun 26.

Differential effects of TGF-beta on connective tissue growth factor (CTGF/CCN2) expression in hepatic stellate cells and hepatocytes.

Author information

  • 1Institute of Clinical Chemistry and Pathobiochemistry, RWTH-University Hospital, D-52074 Aachen, Germany.

Abstract

BACKGROUND/AIMS:

Connective tissue growth factor (CTGF/CCN2) has been implicated in the pathogenesis of hepatic fibrosis and suggested as a downstream mediator of the fibrogenic master cytokine TGF-beta.

METHODS:

We investigated the effect of TGF-beta1 on CTGF/CCN2 expression in cultured rat hepatic stellate cells and hepatocytes by means of Western and Northern blotting, immunocytochemistry, reporter gene analysis, and metabolic labelling.

RESULTS:

We found that the expression of CTGF/CCN2 in hepatic stellate cells is (i) only marginally (if at all) stimulated by TGF-beta and by a constitutively active type I TGF-beta receptor, (ii) independent from Smad2/3 phosphorylation, (iii) not reduced by TGF-beta1 antagonists or ALK5-receptor inhibitors and (iv) not upregulated during transdifferentiation to myofibroblasts in culture. However, expression and secretion of CTGF/CCN2 in cultured hepatocytes increased spontaneously during culture and was strongly stimulated by TGF-beta1. In bile-duct ligated and CCl(4)-treated rat livers, a strong CTGF/CCN2 expression in hepatocytes was noticed. Endothelin-1 stimulated CTGF/CCN2 expression in stellate cells but not in hepatocytes. Pathway specific signalling inhibitors point to the involvement of non-Smad signalling cascades but their contribution to CTGF/CCN2 regulation is different in both cell types.

CONCLUSIONS:

The results do not reveal a relevant interrelation between TGF-beta function and CTGF/CCN2 expression in hepatic stellate cells, which is in contrast to hepatocytes.

PMID:
17629588
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk