Effect of adenovirus-mediated overexpression of decorin on metalloproteinases, tissue inhibitors of metalloproteinases and cytokines secretion by human gingival fibroblasts.
Decorin is a small leucine-rich proteoglycan that plays a role in control of cell proliferation, cell migration, collagen fibrillogenesis and modulation of the activity of TGF-beta. In the present study, we investigated the effects of decorin on the production of metalloproteinases (MMP-1, -2, -3, -9 and -13), tissue inhibitors of metalloproteinases (TIMP-1, -2) and cytokines (TGF-beta, IL-1beta, IL-4 and TNF-alpha). Decorin was overexpressed in cultured human gingival fibroblasts using adenovirus-mediated gene transfer. Decorin infection resulted in decreased protein levels of MMP-1 and MMP-3 whereas MMP-2 and TIMP-2 secretion was increased. MMP-9, MMP-13 and TIMP-1 were not affected by decorin infection. Cytokine measurements by ELISA showed that decorin overexpression reduced TGF-beta and IL-1beta. In contrast, IL-4 and TNF-alpha levels were markedly increased in decorin-infected cells. These results suggest that decorin could modulate the expression of certain metalloproteinases and their inhibitors, as well as the production of cytokines. Altogether, our data suggest that decorin might play a pivotal role in tissue remodeling by acting on the balance between extracellular matrix synthesis and degradation.
Al Haj Zen
Ayman
A
INSERM E-0016, Necker Medical School, 156, Rue de Vaugirard, 75015, Paris, France. aymanzen@aol.com
Lafont
Antoine
A
Durand
Eric
E
Brasselet
Camille
C
Lemarchand
Patricia
P
Godeau
Gaston
G
Gogly
Bruno
B
D000256:Adenoviridae / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D058575:Decorin; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D005881:Gingiva / Q000166:cytology / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis*
D016207:Cytokines; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases