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

Abstract Background 5‐hydroxytryptamine (5‐ HT ) receptors are upregulated in activated hepatic stellate cells ( HSC s), and are therefore thought to play an important role in their activation. Aim The aim of this study was to determine whether 5‐ HT 2A receptor antagonists affect the activation or apoptosis of HSC s 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‐ HT 2A 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‐ HT 2A receptor antagonist (sarpogrelate, 30 mg/kg) was administered. Results 5‐HT 2A , but not 5‐HT 2B receptor mRNA increased with time upon HSC activation. 5‐HT 2A 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‐ HT 2A receptor antagonists can reduce inflammation and the activation of HSC s in this cirrhotic model.