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Ceramide accelerates ultraviolet-induced MMP-1 expression through JAK1/STAT-1 pathway in cultured human dermal fibroblasts
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Sangmin | - |
dc.contributor.author | Kim, Yoonkyung | - |
dc.contributor.author | Lee, Youngae | - |
dc.contributor.author | Chung, Jin Ho | - |
dc.date.accessioned | 2010-06-07T05:24:42Z | - |
dc.date.available | 2010-06-07T05:24:42Z | - |
dc.date.issued | 2008-07-31 | - |
dc.identifier.citation | J Lipid Res. 49(12): 2571-2581 | en |
dc.identifier.issn | 0022-2275 (Print) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18664717 | - |
dc.identifier.uri | http://www.jlr.org/cgi/reprint/49/12/2571.pdf | - |
dc.identifier.uri | https://hdl.handle.net/10371/67536 | - |
dc.description.abstract | 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. | en |
dc.language.iso | en | en |
dc.publisher | American Society for Biochemistry and Molecular Biology | en |
dc.subject | Adult | en |
dc.subject | Cells, Cultured | en |
dc.subject | Ceramidases/antagonists & inhibitors/metabolism | en |
dc.subject | Ceramides/metabolism/*pharmacology | en |
dc.subject | Dermis/cytology/*metabolism | en |
dc.subject | Enzyme Inhibitors/pharmacology | en |
dc.subject | Fibroblasts/cytology/*metabolism | en |
dc.subject | Humans | en |
dc.subject | Janus Kinase 1/antagonists & inhibitors/*metabolism | en |
dc.subject | Janus Kinase 3/antagonists & inhibitors/metabolism | en |
dc.subject | Matrix Metalloproteinase 1/*genetics/metabolism | en |
dc.subject | Phosphorylation | en |
dc.subject | STAT1 Transcription Factor/*metabolism | en |
dc.subject | Sphingomyelin Phosphodiesterase/antagonists & inhibitors/genetics/metabolism | en |
dc.subject | Ultraviolet Rays/adverse effects | en |
dc.subject | Signal Transduction | - |
dc.title | Ceramide accelerates ultraviolet-induced MMP-1 expression through JAK1/STAT-1 pathway in cultured human dermal fibroblasts | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 김상민 | - |
dc.contributor.AlternativeAuthor | 김윤경 | - |
dc.contributor.AlternativeAuthor | 이영애 | - |
dc.contributor.AlternativeAuthor | 정진호 | - |
dc.identifier.doi | 10.1194/jlr.M800112-JLR200 | - |
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