Suppressive effects of leflunomide on leptin-induced collagen I production involved in hepatic stellate cell proliferation.
Exp Biol Med (Maywood)
; 232(3): 427-36, 2007 Mar.
Article
en En
| MEDLINE
| ID: mdl-17327477
ABSTRACT
In this manuscript, we showed that following a fibrogenic stimulus of leptin, hepatic stellate cells (HSCs) underwent a complex activation process characterized by increased proliferation and excessive deposition of type I collagen. Studies with special chemical inhibitors demonstrated that this process involved Janus protein tyrosine kinase (JAK)/signal transducer and activator of transcription (STAT), mitogen-activated protein kinases (MAPK), and phosphatidylinositol 3-linase (PI3K)/Protein kinase B (AKT) signal pathways. Leflunomide pretreatment significantly inhibited the deposition of type I collagen in HSCs and the proliferation of primary HSC by interrupting the three proliferative signal transduction pathways in vitro, which was indicated by [(3)H]thymidine incorporation and cell cycle analysis. Furthermore, leptin-induced cyclin D1 protein expression, which correlates well with HSC proliferation, was also significantly inhibited by leflunomide. On the other hand, leflunomide also prevented leptin-induced Kupffer cell (KC) activation and HSC collagen synthesis induced by KC-conditioned medium (KCCM). Collectively, these results provided a novel insight into the mechanisms by which leflunomide may exert in liver fibrosis.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leptina
/
Colágeno Tipo I
/
Proliferación Celular
/
Isoxazoles
Límite:
Animals
Idioma:
En
Revista:
Exp Biol Med (Maywood)
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
/
MEDICINA
Año:
2007
Tipo del documento:
Article
País de afiliación:
China