Article (Scientific journals)
MMP-9 regulates both positively and negatively collagen gel contraction - A nonproteolytic function of MMP-9
Defawe, Olivier D; Kenagy, Richard D; Choi, Chun et al.
2005In Cardiovascular Research, 66 (2), p. 402-409
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Keywords :
Animals; Aorta; Cell Proliferation/drug effects; Cell Culture Techniques; contraction; matrix metalloproteinase-9; Phenylalanine/analogs & derivatives/pharmacology; Rats, Inbred F344; remodeling; smooth muscle cell; Thiophenes/pharmacology; Tissue Inhibitor of Metalloproteinase-1/pharmacology
Abstract :
[en] Objective: Constrictive remodeling accounts for lumen loss in postangioplasty restenosis. Matrix metalloproteinase-9 (MMP-9) has been shown to prevent constrictive remodeling in vivo. To investigate potential mechanisms for this observation, we investigated the role of MMP-9 in smooth muscle cell (SMC)-mediated collagen gel contraction, an in vitro model of constrictive remodeling. Methods: Fischer rat SMCs were stably transfected with a construct-expressing rat-MMP-9 under the control of a tetracycline (Tet)-off promoter. SMCs were seeded in type 1 collagen gels (2.4 mg/ml) in the presence or not of tetracycline (1 mu g/ml), and gel contraction was defined as the percentage of retraction of the collagen gel. The depletion of MMP-9 was obtained by using siRNA targeting MMP-9 mRNA or a blocking antibody. Results: Gel contraction was significantly reduced at all times when MMP-9 was overexpressed (Tet-) as compared with the control condition (Tet+). However, MMP-9 depletion of control (Tet+) SMCS (using siRNA or antibody) also inhibited gel contraction. To resolve the apparent discrepancy and determine if MMP-9 exerts a dose-dependent biphasic effect on gel contraction, conditioned medium and purified rat-MMP-9 were prepared. Gel contraction was significantly increased by addition of 0.8 mg/ml of MMP-9, while high concentrations of MMP-9 (>= 100 mg/ml) inhibited contraction. The addition of BB94 and TIMP-1 did not alter the inhibitory or stimulatory effect of MMP-9. Conclusions: Our data Suggest that MMP-9, independent of its proteolytic function, has a biphasic effect on SMC-mediated collagen gel contraction. Understanding the different roles of MMP-9 Should allow the development of better therapeutic strategies for restenotic vascular disease. (c) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
Disciplines :
Surgery
Cardiovascular & respiratory systems
Author, co-author :
Defawe, Olivier D;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire deBiologie des Tissus Conjonctifs
Kenagy, Richard D;  University of Washington - Seattle,WA > Division of Vascular Surgery - Dpt of Surgery
Choi, Chun;  University of Washington - Seattle,WA > Division of Vascular Surgery - Dpt of Surgery
Wan, Samuel Y C;  University of Washington - Seattle,WA > Division of Vascular Surgery - Dpt of Surgery
Deroanne, Christophe ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Nusgens, Betty ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
SakalihasanN, Natzi ;  Centre Hospitalier Universitaire de Liège - CHU > Chirurgie cardio-vasculaire
Colige, Alain ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire de BIologie des TissusConjonctifs
Clowes, Alexander W;  University of Washington - Seattle,WA > Division of Vascular Surgery - Dpt of Surgery
Language :
English
Title :
MMP-9 regulates both positively and negatively collagen gel contraction - A nonproteolytic function of MMP-9
Publication date :
2005
Journal title :
Cardiovascular Research
ISSN :
0008-6363
eISSN :
1755-3245
Publisher :
Elsevier Science, Amsterdam, Netherlands
Volume :
66
Issue :
2
Pages :
402-409
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 06 May 2010

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