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

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.