Differential effects of TGF-beta on connective tissue growth factor (CTGF/CCN2) expression in hepatic stellate cells and hepatocytes
| Autor: | Olav A. Gressner, Axel M. Gressner, Ralf Weiskirchen, Birgit Lahme, Ilhan Demirci |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Liver Cirrhosis
medicine.medical_specialty Liver cytology medicine.medical_treatment Receptor Transforming Growth Factor-beta Type I Connective tissue Smad Proteins Biology Protein Serine-Threonine Kinases Immediate-Early Proteins Transforming Growth Factor beta1 Internal medicine medicine Animals RNA Messenger Cells Cultured integumentary system Hepatology Endothelin-1 Growth factor Connective Tissue Growth Factor Molecular biology Rats CTGF medicine.anatomical_structure Cytokine Endocrinology Liver Connective tissue metabolism Connective Tissue Hepatocyte Hepatic stellate cell Hepatocytes Intercellular Signaling Peptides and Proteins Receptors Transforming Growth Factor beta Signal Transduction |
| Zdroj: | Journal of hepatology. 47(5) |
| ISSN: | 0168-8278 |
| Popis: | 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-β. Methods We investigated the effect of TGF-β1 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-β and by a constitutively active type I TGF-β receptor, (ii) independent from Smad2/3 phosphorylation, (iii) not reduced by TGF-β1 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-β1. 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-β function and CTGF/CCN2 expression in hepatic stellate cells, which is in contrast to hepatocytes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect