Matrix metalloproteinase-3 differences in oral and skin fibroblasts.
While skin wounds heal by scarring, wounds of oral mucosa show privileged healing with minimal scar formation. Our hypothesis was that phenotypic differences between oral and skin fibroblasts underlie these differences in healing. The aims of this study were to compare MMP-3 expression by oral and skin fibroblasts and investigate a role for MMP-3 in mediating collagen gel contraction. Oral fibroblasts induced significantly greater gel contraction than did paired skin cells. Inhibition of MMP activity significantly inhibited gel contraction by both cell types. Specific inhibition of MMP-3 activity reduced gel contraction by oral, but not skin, fibroblasts. Oral fibroblasts produced significantly higher levels of MMP-3 than did skin fibroblasts at all levels studied. TGF-beta1 and -beta3 isoforms stimulated MMP-3 expression at mRNA, protein, and activity levels by both fibroblast populations. Results suggest that increased MMP-3 production by oral fibroblasts may underlie the differences in wound-healing outcome seen in skin and oral mucosa.
McKeown
S T W
ST
Oral Science Research Centre, School of Dentistry, Queen's University Belfast, Northern Ireland.
Barnes
J J
JJ
Hyland
P L
PL
Lundy
F T
FT
Fray
M J
MJ
Irwin
C R
CR
D000199:Actins / Q000096:biosynthesis; D000328:Adult; D002478:Cells, Cultured; D024042:Collagen Type I / Q000502:physiology; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis / Q000502:physiology*; D061965:Matrix Metalloproteinase Inhibitors; D009061:Mouth Mucosa / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D020033:Protein Isoforms; D012867:Skin / Q000166:cytology / Q000201:enzymology*; D012879:Skin Physiological Phenomena; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*
D000199:Actins; D024042:Collagen Type I; D061965:Matrix Metalloproteinase Inhibitors; D020033:Protein Isoforms; D016212:Transforming Growth Factor beta; D019278:Matrix Metalloproteinase 3