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Ceramide accelerates ultraviolet-induced MMP-1 expression through JAK1/STAT-1 pathway in cultured human dermal fibroblasts
Cited 30 time in
Web of Science
Cited 31 time in Scopus
- Authors
- Issue Date
- 2008-07-31
- Citation
- J Lipid Res. 49(12): 2571-2581
- Keywords
- 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 ; Sphingomyelin Phosphodiesterase/antagonists & inhibitors/genetics/metabolism ; Ultraviolet Rays/adverse effects ; Signal Transduction
- 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.
- ISSN
- 0022-2275 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18664717
http://www.jlr.org/cgi/reprint/49/12/2571.pdf
https://hdl.handle.net/10371/67536
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