44 0

5-HT2A receptor antagonists inhibit hepatic stellate cell activation and facilitate apoptosis

Title
5-HT2A receptor antagonists inhibit hepatic stellate cell activation and facilitate apoptosis
Author
이항락
Keywords
hepatic stellate cell; fibrosis; sarpogrelate; 5-HT; 5-HT2A receptor
Issue Date
2013-04
Publisher
Blackwell Publishing Ltd
Citation
LIVER INTERNATIONAL, 2013, 33(4), P.535-543
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, -SMA, TGF- 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, 30mg/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 -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 -SMA, TGF- 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.
URI
http://onlinelibrary.wiley.com/doi/10.1111/liv.12110/abstract;jsessionid=E9A778DF1123591C608E538515A3B8F8.f02t02http://hdl.handle.net/20.500.11754/44010
ISSN
1478-3223
DOI
10.1111/liv.12110
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE