Cdc42 inhibits ERK-mediated collagenase-1 (MMP-1) expression in collagen-activated human keratinocytes.
J Invest Dermatol
; 134(5): 1230-1237, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24352036
ABSTRACT
Following injury, keratinocytes switch gene expression programs from the one that promotes differentiation to the one that supports migration. A common feature of human wounds and ulcerations of any form is the expression of matrix metalloproteinase 1 (MMP-1; collagenase-1) by leading-edge basal keratinocytes migrating across the dermal or provisional matrix. Induction of MMP-1 occurs by signaling from the α2ß1 integrin in contact with dermal fibrillar type I collagen, and the activity of MMP-1 is required for human keratinocytes to migrate on collagen. Thus, MMP-1 serves a critical role in the repair of damaged human skin. Here, we evaluated the mechanisms controlling MMP-1 expression in primary human keratinocytes from neonatal foreskin and adult female skin. Our results demonstrate that shortly following contact with type I collagen extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase were markedly activated, whereas c-Jun N-terminal kinase (JNK) phosphorylation remained at basal levels. ERK inhibition markedly blocked collagen-stimulated MMP-1 expression in keratinocytes. In contrast, inhibiting p38 or JNK pathways had no effect on MMP-1 production. Moreover, investigating the role of Rho GTPases revealed that Cdc42 attenuates MMP-1 expression by suppressing ERK activity. Thus, our data indicate that injured keratinocytes induce MMP-1 expression through ERK activation, and this process is negatively regulated by Cdc42 activity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Queratinócitos
/
Movimento Celular
/
Metaloproteinase 1 da Matriz
/
Sistema de Sinalização das MAP Quinases
/
Proteínas Ativadoras de GTPase
/
Colágeno Tipo I
Limite:
Adult
/
Female
/
Humans
/
Male
/
Newborn
Idioma:
En
Revista:
J Invest Dermatol
Ano de publicação:
2014
Tipo de documento:
Article