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. Conclusion: These results suggest that keratinocytes regulate their secretion of MMP-2 and MMP-9 gelatinase in distinct and independent patterns during differentiation.