gms | German Medical Science

102. Jahrestagung der DOG

Deutsche Ophthalmologische Gesellschaft e. V.

23. bis 26.09.2004, Berlin

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TGF-β-mediated MAP-kinase activation in human tenon fibroblasts

Meeting Abstract

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  • T. Meyer-ter-Vehn - Universität Würzburg, Augenklinik und Poliklinik
  • corresponding author P. Knaus - Universität Würzburg, Institut für Physiologische Chemie II
  • corresponding author W. Sebald - Universität Würzburg, Augenklinik und Poliklinik
  • corresponding author F. Grehn - Universität Würzburg, Augenklinik und Poliklinik
  • corresponding author G. Schlunck - Universität Würzburg, Augenklinik und Poliklinik

Evidenzbasierte Medizin - Anspruch und Wirklichkeit. 102. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft. Berlin, 23.-26.09.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04dogP 088

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dog2004/04dog579.shtml

Published: September 22, 2004

© 2004 Meyer-ter-Vehn et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Objective

TGF-β-induced myofibroblast transdifferentiation is an essential step in scar-related filtration bleb failure. We showed previously, that inhibition of p38 mitogen-activated kinase (MAPK) abrogates TGF-β-induced smooth muscle actin (SMA) expression in human tenon fibroblasts. Here, we further characterize TGF-β-mediated p38 activation in this cell type.

Methods

Cultures of human tenon fibroblasts were serum-starved and stimulated with recombinant TGF-β1 to measure subsequent p38 and ERK activation and SMA expression levels by western blot. Suspended and adherent cells were studied to assess the effects of cell adhesion.

Results

TGF-β1-induced p38 activation was biphasic. An early activation phase subsided after 6hrs and was followed by a sustained secondary phase of p38 phosphorylation that was detectable at 12hrs and continued in the presence of TGF. In contrast, ERK showed an early transient phosphorylation. An increase in SMA expression coincides with the secondary p38 phosphorylation. TGF-β1-mediated p38 activation was adhesion-dependent as suspended cells showed no p38 or ERK phosphorylation after stimulation.

Conclusions

The time course of TGF-β1-induced p38 phosphorylation is compatible with an autocrine late phase stimulation mechanism which was shown to drive TGF-β-dependent antiapoptotic signaling in mesenchymal cells. The adhesion-dependence of TGF-β-induced p38 phosphorylation illustrates the importance of signal integration and indicates how alterations in extracellular matrix composition may affect wound healing responses.