文章基本信息

标题：Ceramide accelerates ultraviolet-induced MMP-1 expression through JAK1/STAT-1 pathway in cultured human dermal fibroblasts
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作者：Sangmin Kim ; Yoonkyung Kim ; Youngae Lee 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2008
卷号：49
期号：12
页码：2571-2581
DOI：10.1194/jlr.M800112-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：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 C₂-ceramide or SMase treatment. The activation of ceramide pathway by C₂-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.