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International Journal of Colorectal Disease

Published in:

01-09-2004 | Original Article

Involvement of AP-1 proteins in pancreatic stellate cell activation in vitro

Authors: Brit Fitzner, Gisela Sparmann, Jörg Emmrich, Stefan Liebe, Robert Jaster

Published in: International Journal of Colorectal Disease | Issue 5/2004

Abstract

Background and aims

Pancreatic stellate cells (PSCs) play a key role in the development of pancreatic fibrosis. The molecular mechanisms underlying their activation in response to profibrogenic mediators, however, are largely unknown. Extending previous studies on the transcriptional regulation of PSC activation, we have now focused on the involvement of activator protein (AP)-1.

Materials and methods

Using cultured rat PSCs, phenotypic transition of PSCs towards activated myofibroblasts was monitored by an immunoblot analysis of α-smooth muscle actin (α-SMA) expression. Transcription factor activation profiles were studied by electrophoretic mobility shift assays. DNA synthesis in PSCs was assessed through the quantification of 5-bromo-2’-deoxyuridine incorporation.

Results

Activated AP-1 complexes were detectable already before high levels of α-SMA were expressed. Maximal DNA binding activity of AP-1, as well as of NF-κB, was observed early in the course of PSC culture, while the strongest activation of STAT3 was observed much later. A detailed analysis of AP-1 complex composition revealed that phenotypic transition of PSCs towards myofibroblasts was accompanied by an increase of the JunD content relative to the one of JunB. Studies on the role of JunB and JunD in PSC activation indicated an inhibition of platelet-derived growth factor-induced DNA synthesis by antisense oligonucleotides to JunB but not JunD.

Conclusions

The results of this study implicate AP-1 in PSC activation and suggest distinct roles of individual Jun proteins in the regulation of PSC function. In further studies, it should be analyzed whether signaling pathways involved in PSC activation might be suitable targets for antifibrotic therapies.

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Title: Involvement of AP-1 proteins in pancreatic stellate cell activation in vitro
Authors: Brit Fitzner
Gisela Sparmann
Jörg Emmrich
Stefan Liebe
Robert Jaster
Publication date: 01-09-2004
Publisher: Springer-Verlag
Published in: International Journal of Colorectal Disease / Issue 5/2004
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-003-0565-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Involvement of AP-1 proteins in pancreatic stellate cell activation in vitro

Abstract

Background and aims

Materials and methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and aims

Materials and methods

Results

Conclusions

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