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Comparative Hepatology
Published in: Comparative Hepatology 1/2007

Open Access 01-12-2007 | Research

Glucocorticoids activate TGF-β induced PAI-1 and CTGF expression in rat hepatocytes

Authors: Lucia Wickert, Nicolas Chatain, Karin Kruschinsky, Axel M Gressner

Published in: Comparative Hepatology | Issue 1/2007

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Abstract

Background

In addition to the activation of hepatic stellate cells TGF-β govern apoptosis and growth control of hepatocytes in liver injury. In non-parenchymal cells, TGF-β induces plasminogen activator inhibitor 1 (PAI-1) and connective tissue growth factor (CTGF) expression, which are involved in extra cellular matrix formation. Both genes were also regulated by glucocorticoids, which in certain cases showed antagonistic effects to the TGF-β-Smad 3 pathway. The purpose of our work was to investigate the influence of TGF-β and dexamethasone on PAI-1 and CTGF expression and secretion in primary hepatocytes.

Results

By examining PAI-1 and CTGF mRNA and protein expression in cell lysates and cell-conditioned media under the influence of TGF-β and dexamethasone, we analysed signalling pathways controlling their expression. TGF-β and dexamethasone significantly co-induce PAI-1 and CTGF protein expression. On the other hand, we showed that TGF-β diminished a glucocorticoid receptor dependent luciferase reporter signal in Hep-G2. Inhibition of Erk downstream activation decreased TGF-β induced CTGF and PAI-1 expression to a basal level. PAI-1 was directly secreted by hepatocytes, whereas secretion of CTGF was retarded.

Conclusion

The data provide evidence that beside the TGF-β-Smad 3 pathway CTGF and PAI-1 expression is additionally dependent on Erk activity in hepatocytes giving new insights into regulation of the profibrogenic proteins.
Appendix
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Metadata
Title
Glucocorticoids activate TGF-β induced PAI-1 and CTGF expression in rat hepatocytes
Authors
Lucia Wickert
Nicolas Chatain
Karin Kruschinsky
Axel M Gressner
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Comparative Hepatology / Issue 1/2007
Electronic ISSN: 1476-5926
DOI
https://doi.org/10.1186/1476-5926-6-5

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