QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online November 3, 2003
doi: 10.1242/10.1242/jcs.00808

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tufvesson, E. Articles by Westergren-Thorsson, G. Search for Related Content PubMed PubMed Citation Articles by Tufvesson, E. Articles by Westergren-Thorsson, G.

Biglycan and decorin induce morphological and cytoskeletal changes involving signalling by the small GTPases RhoA and Rac1 resulting in lung fibroblast migration

Section for Cell and Matrix Biology, Department of Cell and Molecular Biology, BMC C13, Lund University, 221 84 Lund, Sweden

^* Author for correspondence (e-mail: Ellen.Tufvesson{at}medkem.lu.se)

Accepted 28 July 2003

Biglycan and decorin are small chondroitin/dermatan sulphate proteoglycans in the extracellular matrix of connective tissue that belong to the family of structurally related proteoglycans called small leucine-rich repeat proteins.

We show for the first time that biglycan and decorin induce morphological and cytoskeletal changes in fibroblasts, resulting in an increase in migration. Biglycan changed the cell shape of fibroblasts with formation of long protruding filamentous processes. This was also seen for decorin but to a lesser extent. Using fluorescence staining of F-actin fibres it was possible to show that these long filamentous processes were supported by long thick bundles of actin, together with an induced formation of stress fibres after stimulation with biglycan and decorin. Moreover, a reorganisation of -smooth muscle actin was clearly seen in these cultures. Decorin also stimulated -smooth muscle actin expression in the cells. Using cDNA Atlas Arrays we were also able to show that the mRNA level of a number of the intracellular regulators and effectors involved in cell migration were increased. For example, the focal adhesion proteins paxillin and zyxin, and some of the small Rho GTPases such as RhoA, Rac1 and Cdc42 were upregulated. After treatment with biglycan or decorin, additional results showed an increased activation of RhoA (1.8- and 1.5-fold, respectively) and Rac1 (1.8- and 1.5-fold, respectively) after 15 minutes. These factors are known to be involved in fibroblast migration, and as expected a 1.3- to 1.6-fold increase in migration could be observed after stimulation with biglycan or decorin. This induced migration was caused by the core protein, as treatment with glycosaminoglycan chains alone did not have any effect.

In summary, these data indicate that biglycan- and decorin-induced fibroblast cytoskeletal and signalling changes result in an increased cell migration, and demonstrate their potential role in the remodelling process.

Key words: Biglycan, Decorin, Cytoskeleton, Fibroblast, Migration, Rho GTPases

This article has been cited by other articles:

				L. R. Fiedler, E. Schonherr, R. Waddington, S. Niland, D. G. Seidler, D. Aeschlimann, and J. A. Eble Decorin Regulates Endothelial Cell Motility on Collagen I through Activation of Insulin-like Growth Factor I Receptor and Modulation of {alpha}2{beta}1 Integrin Activity J. Biol. Chem., June 20, 2008; 283(25): 17406 - 17415. [Abstract] [Full Text] [PDF]

				A. Scheja, K. Larsen, L. Todorova, E. Tufvesson, M. Wildt, A. Akesson, L. Hansson, S. Ellis, and G. Westergren Thorsson BALF-derived fibroblasts differ from biopsy-derived fibroblasts in systemic sclerosis Eur. Respir. J., March 1, 2007; 29(3): 446 - 452. [Abstract] [Full Text] [PDF]

				L. Pini, C. Torregiani, J. G. Martin, Q. Hamid, and M. S. Ludwig Airway remodeling in allergen-challenged Brown Norway rats: distribution of proteoglycans Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1052 - L1058. [Abstract] [Full Text] [PDF]

				L. Todorova, E. Gurcan, A. Miller-Larsson, and G. Westergren-Thorsson Lung Fibroblast Proteoglycan Production Induced by Serum Is Inhibited by Budesonide and Formoterol Am. J. Respir. Cell Mol. Biol., January 1, 2006; 34(1): 92 - 100. [Abstract] [Full Text] [PDF]

				S. Groth, M. Schulze, H. Kalthoff, F. Fandrich, and H. Ungefroren Adhesion and Rac1-dependent Regulation of Biglycan Gene Expression by Transforming Growth Factor-{beta}: EVIDENCE FOR OXIDATIVE SIGNALING THROUGH NADPH OXIDASE J. Biol. Chem., September 30, 2005; 280(39): 33190 - 33199. [Abstract] [Full Text] [PDF]

				K. Larsen, E. Tufvesson, J. Malmstrom, M. Morgelin, M. Wildt, A. Andersson, A. Lindstrom, A. Malmstrom, C.-G. Lofdahl, G. Marko-Varga, et al. Presence of Activated Mobile Fibroblasts in Bronchoalveolar Lavage from Patients with Mild Asthma Am. J. Respir. Crit. Care Med., November 15, 2004; 170(10): 1049 - 1056. [Abstract] [Full Text] [PDF]