A new selective vascular endothelial growth factor receptor 2 inhibitor ablates disease in a mouse model of psoriasis.
Mol Med Rep
; 8(2): 434-8, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23732650
ABSTRACT
Psoriasis is a common chronic inflammatory skin disease and its underlying pathogenesis is still not fully understood. Therapeutic interventions are currently limited and restricted to the treatment of symptoms rather than targeting the mechanisms underlying the disease. Vascular remodeling is a hallmark of psoriasis; however, anti-vascular strategies to treat psoriasis have received little attention to date, particularly systemic treatment with a small molecule compound. The aim of this study was to investigate the anti-inflammatory effect of a newly identified vascular endothelial growth factor (VEGF) receptor 2 inhibitor, SKLB1002, and its possible mechanism of action in a transgenic mouse model of psoriasis. Fifteen 8-12-weekold K14-VEGF transgenic mice received consecutive intraperitoneal (i.p.) injections of SKLB1002, vehicle or saline for 4 weeks. After 4 weeks of treatment, the disease symptoms were assessed and histological analyses were performed on ear sections by hematoxylin and eosin (HE) and immunohistochemistry staining. Systemic treatment with SKLB1002 reduced symptoms of ear inflammation in K14/VEGF transgenic mice, the pathological score was significantly decreased, and acanthosis, focal parakeratosis, hyperkeratosis and hemangiectasis were improved. Furthermore, systemic treatment with SKLB1002 significantly reduced vascular abnormalities, permeability and T-cell infiltration. These results demonstrated that targeted inhibition of VEGFR2 by a small molecule inhibitor is an effective method, which may be a new therapeutic option for psoriasis therapy.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Psoríase
/
Quinazolinas
/
Tiadiazóis
/
Receptor 2 de Fatores de Crescimento do Endotélio Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2013
Tipo de documento:
Article