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Ceramide accelerates ultraviolet-induced MMP-1 expression through JAK1/STAT-1 pathway in cultured human dermal fibroblasts
Open accessAbstract
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.
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MMP-2 was used as a loading control for MMP-1 western blots because MMP-2 protein levels are not affected by UVB exposure.
“MMP-2 was used as a loading control for MMP-1 western blots, because MMP-2 protein levels are not affected by UVB exposure [17].”
From Anti-Photoaging and Anti-Melanogenic Effects of a Novel Lactiplantibacillus plantarum RKBP Isolated from Giant Centella asiatica (2026) · cites this paper as [17]
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Metadata
- Authors
- Kim, S., Kim, Y., Lee, Y., & Chung, J. H.
- Affiliations
- Seoul National University (KR)
- Corresponding author
- Chung, Jin Ho
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 49
- Issue
- 12
- Pages
- 2571-2581
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W2005723593
- Cited by
- 38
- References
- 43
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 3 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 1
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- ceramide, UV irradiation, MMP-1, human dermal fibroblasts, acid sphingomyelinase, ceramidase, skin aging, piceatannol, JAK3 inhibition
- MeSH terms
- Adult, Cells, Cultured, Ceramides, Enzyme Inhibitors, Fibroblasts, Humans, Phosphorylation, Sphingomyelin Phosphodiesterase, Ultraviolet Rays, Signal Transduction, Dermis, Matrix Metalloproteinase 1, STAT1 Transcription Factor, Janus Kinase 1, Janus Kinase 3, Ceramidases
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