Induction and repression of collagenase-1 by keratinocytes is controlled by distinct components of different extracellular matrix compartments.
In all forms of cutaneous wounds, collagenase-1 (matrix metalloproteinase-1 (MMP-1)) is invariably expressed by basal keratinocytes migrating over the dermal matrix. We report that native type I collagen mediates induction of MMP-1 by primary human keratinocytes. Collagen-mediated induction of MMP-1 was rapid, being detected 2 h after plating, and was transcriptionally regulated. As demonstrated by in situ hybridization, only migrating keratinocytes expressed MMP-1, suggesting that contact with collagen is not sufficient to induce MMP-1 expression in keratinocytes; the cells must also be migrating. Upon denaturation, type I collagen lost its ability to induce MMP-1 expression but still supported cell adhesion. Other dermal or wound matrix proteins, such as type III collagen, fibrin, and fibronectin, and a mixture of basement membrane proteins did not induce MMP-1 production. In the presence of collagen, laminin-1 inhibited induction of MMP-1 but laminin-5 did not. Taken together, these observations suggest that as basal keratinocytes migrate from the basal lamina onto the dermal matrix contact with native type I collagen induces MMP-1 expression. In addition, our findings suggest that re-establishment of the basement membrane and, in particular, contact with laminin-1 provides a potent signal to down-regulate MMP-1 production as the epithelium is repaired.
Sudbeck
B D
BD
Department of Medicine (Dermatology), Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Pilcher
B K
BK
Welgus
H G
HG
Parks
W C
WC
D002448:Cell Adhesion; D002451:Cell Compartmentation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004790:Enzyme Induction; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology*; D020781:Matrix Metalloproteinase 1; D011401:Promoter Regions, Genetic; D014945:Wound Healing
D003094:Collagen; D017364:Collagenases; D020781:Matrix Metalloproteinase 1