S-Space College of Medicine/School of Medicine (의과대학/대학원) Dermatology (피부과학전공) Journal Papers (저널논문_피부과학전공)
Ceramide accelerates ultraviolet-induced MMP-1 expression through JAK1/STAT-1 pathway in cultured human dermal fibroblasts
- Kim, Sangmin; Kim, Yoonkyung; Lee, Youngae; Chung, Jin Ho
- Issue Date
- J Lipid Res. 49(12): 2571-2581
- Adult; Cells, Cultured; Ceramidases/antagonists & inhibitors/metabolism; Ceramides/metabolism/*pharmacology; Dermis/cytology/*metabolism; Enzyme Inhibitors/pharmacology; Fibroblasts/cytology/*metabolism; Humans; Janus Kinase 1/antagonists & inhibitors/*metabolism; Janus Kinase 3/antagonists & inhibitors/metabolism; Matrix Metalloproteinase 1/*genetics/metabolism; Phosphorylation; STAT1 Transcription Factor/*metabolism; *Signal Transduction; Sphingomyelin Phosphodiesterase/antagonists & inhibitors/genetics/metabolism; Ultraviolet Rays/adverse effects
- 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 matrix metalloproteinase-1 (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 UV-induced MMP-1 expression. On the other hand, 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 dose-dependently increased by C(2)-ceramide or SMase treatment. The activation of ceramide pathway by C(2)-ceramide enhanced phosphorylation of signal transducer and activators of transcription-1 (STAT-1), whereas ceramide-induced MMP-1 expression was potently prevented by piceatannol; Janus kinase (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 UV-induced 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.
- 0022-2275 (Print)
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