Ceramide accelerates ultraviolet (UV)-induced MMP-1 expression through JAK1/STAT-1 pathway in cultured human dermal fibroblasts

Kim, S. etc
Journal of Lipid Research, 2008

Ultraviolet (UV) irradiation accelerates formation of ceramide through hydrolysis of
sphingomyelin and de novo synthesis. Here, we investigated the effects of ceramide on
UV-induced MMP-1 expression in human dermal fibroblasts. Our results showed that
acidic-sphingomyelinase (aSMase) and MMP-1 mRNA expression were increased by UV
irradiation. Treatment of D609 (aSMase inhibitor) decreased the level of basal and UVinduced
MMP-1 expression. On the other hand, both basal and UV-induced MMP-1
expression was increased through induction of intracellular ceramide by D-MAPP, a
ceramidase inhibitor. Our results also showed that MMP-1 protein expression was dosedependently
increased by C2
-ceramide or SMase treatment. The activation of ceramide
pathway by C2
-ceramide enhanced phosphorylation of STAT-1, whereas ceramide-induced
MMP-1 expression was potently prevented by piceatannol, JAK1 inhibtor, and WHI-P131,
a specific inhibitor of JAK3, but not by AG490, JAK 2 inhbitor, in human dermal
fibroblasts. We also found that UV induced the phosphorylation of STAT-1 and UVinduced
MMP-1 expression was significantly decreased by JAK1 inhibitor, piceatannol.
Overall, we demonstrate that induction of intracellular ceramide by UV may activate
MMP-1 gene expression via JAK1/STAT-1 pathway. Therefore, we suggest that targeted
modulation of the ceramide signaling pathway may offer a novel therapeutic approach for
inhibiting MMP-1 expression which is a causing gene of skin aging.

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Journal of Lipid Research
Seoul National University