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
최호순
Keywords
hepatic stellate cell; fibrosis; sarpogrelate; 5-HT; 5-HT2A receptor
Issue Date
2013-03
Publisher
Wiley-Blackwell
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, α- SMA, TGF-β 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-β 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
https://onlinelibrary.wiley.com/doi/abs/10.1111/liv.12110http://hdl.handle.net/20.500.11754/52181
ISSN
1478-3223; 1478-3231
DOI
10.1111/liv.12110
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > ETC
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