Browse

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

Cited 25 time in Web of Science Cited 27 time in Scopus
Authors
Kim, Sangmin; Kim, Yoonkyung; Lee, Youngae; Chung, Jin Ho
Issue Date
2008-07-31
Publisher
American Society for Biochemistry and Molecular Biology
Citation
J Lipid Res. 49(12): 2571-2581
Keywords
AdultCells, CulturedCeramidases/antagonists & inhibitors/metabolismCeramides/metabolism/*pharmacologyDermis/cytology/*metabolismEnzyme Inhibitors/pharmacologyFibroblasts/cytology/*metabolismHumansJanus Kinase 1/antagonists & inhibitors/*metabolismJanus Kinase 3/antagonists & inhibitors/metabolismMatrix Metalloproteinase 1/*genetics/metabolismPhosphorylationSTAT1 Transcription Factor/*metabolism*Signal TransductionSphingomyelin Phosphodiesterase/antagonists & inhibitors/genetics/metabolismUltraviolet Rays/adverse effects
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
DOI
https://doi.org/10.1194/jlr.M800112-JLR200
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dermatology (피부과학전공)Journal Papers (저널논문_피부과학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse