IFI27, a novel epidermal growth factor-stabilized protein, is functionally involved in proliferation and cell cycling of human epidermal keratinocytes.
Cell Prolif
; 48(2): 187-97, 2015 Apr.
Article
en En
| MEDLINE
| ID: mdl-25664647
ABSTRACT
OBJECTIVES:
IFI27 is highly expressed in psoriatic lesions but its function has not been known. The present study aimed to explore its role in proliferation of epidermal keratinocytes. MATERIALS ANDMETHODS:
IFI27 knockdown and over-expression in keratinocytes were used to compare their proliferation, by MTT assay, apoptosis (by annexin V binding) and cell cycle progression by flow cytometry. Formation of cyclin A/CDK1 complex was examined by a co-immunoprecipitaion method. Anti-proliferation effects of IFI27 were also examined in vivo by topical application of IFI27 siRNA on imiquimod-induced psoriatic lesions, in a mouse model.RESULTS:
Epidermal growth factor was demonstrated to increase IFI27 expression by prolonging half-life of IFI27 protein. The IFI27 knockdown in keratinocytes reduced the proliferation rate, but had no effect on apoptosis nor on apoptosis-related genes. Interestingly, IFI27 knockdown resulted in S-phase arrest that was found to be associated with increased Tyr15 phosphorylation of CDK1, reduced CDC25B and reduced formation of cyclin A/CDK1 complex. In addition, IFI27 knockdown was also shown to activate p53 by Ser15 phosphorylation and increase p21 expression. Topical application of IFI27 siRNA on imiquimod-induced psoriatic lesion in a mouse model reduced epidermal thickness, formation of rete ridges and PCNA expression.CONCLUSIONS:
Our study demonstrates for the first time, that cell function of IFI27 is involved in proliferation of skin keratinocytes both in vitro and in vivo. It suggests that IFI27 might be a suitable target for development of a novel anti-psoriasis therapy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_skin_diseases
Asunto principal:
Psoriasis
/
Queratinocitos
/
Proliferación Celular
/
Proteínas de la Membrana
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cell Prolif
Año:
2015
Tipo del documento:
Article
País de afiliación:
Taiwán