Abstract | OBJECTIVE: METHODS: RESULTS:
Simvastatin did not cause morphologic changes or cytotoxicity in the fibroblasts, even after 4 days of treatment. Type I collagen production and mRNA levels showed a potent and dose-related inhibition following 3 and 4 days of treatment. The inhibition of collagen gene expression by simvastatin was completely reversed by mevalonate and GGPP, but not by FPP. The statin effects occurred at the transcriptional level and involved the proximal COL1A1 promoter region encompassing -174 bp. A significant reduction in Sp1 and CBF binding activity was also found in simvastatin-treated cells. CONCLUSION:
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Authors | Natalia Louneva, Gonzalo Huaman, Joanna Fertala, Sergio A Jiménez |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 54
Issue 4
Pg. 1298-308
(Apr 2006)
ISSN: 0004-3591 [Print] United States |
PMID | 16575855
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Collagen Type I
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Simvastatin
|
Topics |
- Cells, Cultured
- Collagen Type I
(biosynthesis, drug effects)
- Fibroblasts
(drug effects, metabolism)
- Gene Expression
(drug effects)
- Humans
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
(pharmacology)
- Scleroderma, Systemic
(genetics, metabolism)
- Simvastatin
(pharmacology)
- Skin
(cytology)
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