Differential regulation of MMP-2 and MMP-9 gelatinases in cultured human keratinocytes.
BACKGROUND
Among matrix metalloproteinases (MMPs), MMP-2 and MMP-9 are considered to play important roles in the tissue metabolism.


OBJECTIVE
To study the production of MMP-2 and MMP-9 in cultured keratinocytes.


METHODS
We examined the effect of cell passage number and cell differentiation on these enzymes by zymography and immunocytochemistry.


RESULTS
Both MMP-2 and MMP-9 gelatinases were detected in keratinocyte-conditioned media using zymography. The level of MMP-2 in the medium decreased after sequential passage, whereas MMP-9 was detected at a constant level. Treatment of keratinocytes with Ca2+, a potent stimulator for cell differentiation. induced secretion of MMP-9, which was confirmed immunocytochemically. Inversely, treatment with retinoic acid, which inhibits cell differentiation, increased the level of MMP-2.


CONCLUSIONS
These results suggest that keratinocytes regulate their secretion of MMP-2 and MMP-9 gelatinase in distinct and independent patterns during differentiation.
Kobayashi
T
T
Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
Hattori
S
S
Nagai
Y
Y
Tajima
S
S
Nishikawa
T
T
D002118:Calcium / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis*; D018093:Gelatinases / Q000096:biosynthesis* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology*; D007641:Keratolytic Agents / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D014212:Tretinoin / Q000494:pharmacology*
D007641:Keratolytic Agents; D014212:Tretinoin; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D002118:Calcium