Decorin inhibits macrophage colony-stimulating factor proliferation of macrophages and enhances cell survival through induction of p27Kip1 and p21Waf1

Decorin is a small proteoglycan that is ubiquitous in the extracellular matrix of mammalian tissues. It has been extensively demonstrated that decorin inhibits tumor cell growth; however, no data have been reported on the effects of decorin in normal cells. Using nontransformed macrophages from bone...

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Bibliographic Details
Published in:Blood 2001-10, Vol.98 (7), p.2124-2133
Main Authors: Xaus, Jordi, Comalada, Mònica, Cardó, Marina, Valledor, Annabel F., Celada, Antonio
Format: Article
Language:English
Subjects:
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Immunobiology
Monocytes, macrophages
Myeloid cells: ontogeny, maturation, markers, receptors
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Summary:Decorin is a small proteoglycan that is ubiquitous in the extracellular matrix of mammalian tissues. It has been extensively demonstrated that decorin inhibits tumor cell growth; however, no data have been reported on the effects of decorin in normal cells. Using nontransformed macrophages from bone marrow, results of this study showed that decorin inhibits macrophage colony-stimulating factor (M-CSF)–dependent proliferation by inducing blockage at the G1 phase of the cell cycle without affecting cell viability. In addition, decorin rescues macrophages from the induction of apoptosis after growth factor withdrawal. Decorin induces the expression of the cdk inhibitors p21Waf1 and p27Kip1. Using macrophages from mice where these genes have been disrupted, inhibition of proliferation mediated by decorin is related to p27Kip1 expression, whereas p21Waf1expression is necessary to protect macrophages from apoptosis. Decorin also inhibits M-CSF–dependent expression of MKP-1 and extends the kinetics of ERK activity, which is characteristic when macrophages become activated instead of proliferating. The effect of decorin on macrophages is not due to its interaction with epidermal growth factor or interferon-γ receptors. Furthermore, decorin increases macrophage adhesion to the extracellular matrix, and this may be partially responsible for the expression of p27Kip1 and the modification of ERK activity, but not for the increased cell survival.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V98.7.2124