5-HT2A receptor antagonists inhibit hepatic stellate cell activation and facilitate apoptosis.
Liver Int
; 33(4): 535-43, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23362947
ABSTRACT
BACKGROUND:
5-hydroxytryptamine (5-HT) receptors are upregulated in activated hepatic stellate cells (HSCs), and are therefore thought to play an important role in their activation.AIM:
The aim of this study was to determine whether 5-HT2A receptor antagonists affect the activation or apoptosis of HSCs in vitro and/or in vivo.METHODS:
For the in vitro experiments, the viability, apoptosis and wound healing ability of LX-2 cells were examined after treatment with various 5-HT2A receptor antagonists. Levels of HSC activation markers (procollagen type I, α-SMA, TGF-ß and Smad 2/3) were measured. For in vivo experiments, rats were divided into three groups (i) a control group, (ii) a disease group, in which cirrhosis was induced by thioacetamide (iii) a treatment group, in which cirrhosis was induced and a 5-HT2A receptor antagonist (sarpogrelate, 30 mg/kg) was administered.RESULTS:
5-HT2A , but not 5-HT2B receptor mRNA increased with time upon HSC activation. 5-HT2A receptor antagonists (ketanserin and sarpogrelate) inhibited viability and wound healing in LX-2 cells and induced apoptosis. Expression of α-SMA and procollagen type I was also inhibited. In the in vivo study, lobular inflammation was reduced in the sarpogrelate-treated group, but there was only slight and statistically insignificant attenuation of periportal fibrosis. Expression of α-SMA, TGF-ß and Smad 2/3 was also reduced in the treatment group.CONCLUSIONS:
5-HT2A receptor antagonists can reduce inflammation and the activation of HSCs in this cirrhotic model.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Receptor 5-HT2A de Serotonina
/
Células Estreladas do Fígado
/
Antagonistas do Receptor 5-HT2 de Serotonina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Liver Int
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2013
Tipo de documento:
Article