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Rimonabant inhibits proliferation, collagen secretion and induces apoptosis in hepatic stellate cells

Dai, E.; Zhang, J.; Zhang, D.; Yang, L.; Wang, Y.; Jiang, X.; Ye, L.; Li, X.; Liu, H.; Ma, J.; Jiang, H.

Hepato-Gastroenterology 61(135): 2052-2061

2014

ISSN/ISBN: 0172-6390
PMID: 25713910
Document Number: 16842
Liver fibrosis represents a significant health problem worldwide. Hepatic stellate cells (HSCs) play a critical role in the live fibrosis. Rimonabant (SR141716) is cannabinoid receptor type 1 (CB1) antagonist. The pharmacological effects of rimonabant on HSCs are not well characterized in HSCs. CB1 receptor was detected by immunohistochemistry in human liver fibrosis specimens. Cell proliferation was detected by MTT assay. Cell apoptosis, caspase-3 protein expression and cell cycle were detected by TEM and flow cytometry, respectively. Caspase-3 activity was measured using caspase-3 activity assay kit. Collagen secretion was evaluated by radioimmunoassay. CB1 receptor and signaling molecules were evaluated by qRTPCR and Western blot. Immunohistochemistry showed a discrete, punctuated CB1 immunoreactivity in human liver fibrosis specimens. Rimonabant reduced HSC proliferation and increased HSC apoptosis. Cell cycle analysis showed a decrease in G2/M phase cells and an increase in G0/G1 phase cells in HSC-T6 cells treated with rimonabant. Caspase-3 protein expression and activity were increased by rimonabant. Rimonabant decreased collagen secretion in HSC-T6 cells. Moreover, rimonabant inhibited the expression of phosphorylated FAK and ERK and down-regulated CB1 mRNA expression. The study provides new insights toward the pharmacological effect of rimonabant on HSCs in vitro. Rimonabant inhibits proliferation, collagen secretion and induces apoptosis in HSCs.

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Rimonabant inhibits proliferation, collagen secretion and induces apoptosis in hepatic stellate cells

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