SIRT1 modulates expression of matrix metalloproteinases in human dermal fibroblasts.
Br J Dermatol
; 163(4): 689-94, 2010 Oct.
Article
em En
| MEDLINE
| ID: mdl-20426787
ABSTRACT
BACKGROUND:
SIRT1, an NAD(+) -dependent histone/protein deacetylase, controls a broad range of cellular functions.OBJECTIVES:
We examined if SIRT1 is involved in the regulation of matrix metalloproteinase (MMP) expression in human dermal fibroblasts.METHODS:
We studied the effect of inhibition of SIRT1 by specific inhibitor and small interfering RNA (siRNA) on MMP-1 and MMP-3 expression in human dermal fibroblasts.RESULTS:
Treatment with a potent and selective inhibitor of SIRT1, EX-527, increased the basal expression levels of MMP-1 and MMP-3 proteins. Knockdown of endogenous SIRT1 by siRNA led to increased expression of MMP-1 and MMP-3 at both mRNA and protein levels. SIRT1 knockdown also upregulated MMP protein induction caused by an inflammatory cytokine, interleukin (IL)-1ß. Moreover, treatment with a SIRT1 activator, resveratrol, significantly suppressed IL-1ß-mediated induction of MMP-1, which was attenuated by pretreatment with EX-527. Finally, MMP-1 promoter activity was increased by EX-527 in cells treated with or without IL-1ß.CONCLUSIONS:
Our findings suggest that SIRT1 exerts a negative regulatory role in the production of MMP-1 and MMP-3 in human dermal fibroblasts.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pele
/
Metaloproteinases da Matriz
/
Sirtuína 1
/
Fibroblastos
Limite:
Humans
Idioma:
En
Revista:
Br J Dermatol
Ano de publicação:
2010
Tipo de documento:
Article