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.
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.
Authors: Julian M Yabut; Justin D Crane; Alexander E Green; Damien J Keating; Waliul I Khan; Gregory R Steinberg Journal: Endocr Rev Date: 2019-08-01 Impact factor: 19.871
Authors: Carmel B Nanthakumar; Richard J D Hatley; Seble Lemma; Jack Gauldie; Richard P Marshall; Simon J F Macdonald Journal: Nat Rev Drug Discov Date: 2015-09-04 Impact factor: 84.694
Authors: Jörg H W Distler; Andrea-Hermina Györfi; Meera Ramanujam; Michael L Whitfield; Melanie Königshoff; Robert Lafyatis Journal: Nat Rev Rheumatol Date: 2019-11-11 Impact factor: 20.543