Fibroblasts are multifunctional cells that are responsible for matrix homoeostasis, continuously synthesizing and degrading a diverse group of extracellular molecules and their receptors. Rates of turnover of matrix molecules and the proteases that degrade them are normally under the control of diverse chemical and mechanical cues, with cytokines, growth factors, proteases, lipid mediators and mechanical forces playing roles. The maintenance of this homoeostasis is vital to the preservation of normal tissue function and is clearly lost in chronic diseases of the joints, skin and internal organs where destruction and excessive deposition is seen. Current research is focusing on defining the key pathways of activation either in resident fibroblasts, matrix-producing cells derived from circulating fibrocytes, or from transdifferentiation of resident cells. The common downstream signalling pathways are also being defined, as well as the gene interactions leading to altered cell phenotype. The present article reviews these findings and our current concepts of the key molecular events leading to tissue damage and excessive matrix deposition in tissue fibrosis. These studies are leading to an appreciation of the complexity of events with multiple pathways involved, but, as the facts emerge, we are finding promising new ways to treat fibrosis and halt the inexorable progression that is a feature of so many fibrotic and remodelling disorders.
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August 2007
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Conference Article|
July 20 2007
Regulation of matrix turnover: fibroblasts, forces, factors and fibrosis
G.J. Laurent;
G.J. Laurent
1
1Centre for Respiratory Research, Rayne Institute, Royal Free and University College Medical School, 5 University Street, London WC1E 6JJ, U.K.
1To whom correspondence should be addressed (email gjloffice@ucl.ac.uk).
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R.C. Chambers;
R.C. Chambers
1Centre for Respiratory Research, Rayne Institute, Royal Free and University College Medical School, 5 University Street, London WC1E 6JJ, U.K.
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M.R. Hill;
M.R. Hill
1Centre for Respiratory Research, Rayne Institute, Royal Free and University College Medical School, 5 University Street, London WC1E 6JJ, U.K.
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R.J. McAnulty
R.J. McAnulty
1Centre for Respiratory Research, Rayne Institute, Royal Free and University College Medical School, 5 University Street, London WC1E 6JJ, U.K.
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Publisher: Portland Press Ltd
Received:
March 26 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (4): 647–651.
Article history
Received:
March 26 2007
Citation
G.J. Laurent, R.C. Chambers, M.R. Hill, R.J. McAnulty; Regulation of matrix turnover: fibroblasts, forces, factors and fibrosis. Biochem Soc Trans 1 August 2007; 35 (4): 647–651. doi: https://doi.org/10.1042/BST0350647
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