title: Rimonabant inhibits proliferation, collagen secretion and induces apoptosis in hepatic stellate cells.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Erhei
authors.initials: E
authors.lastname: Dai
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Jiang
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Li
authors.forename: Huimin
authors.initials: H
authors.lastname: Liu
authors.forename: Junji
authors.initials: J
authors.lastname: Ma
authors.forename: Huiqing
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010766:Phosphorylation; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000077285:Rimonabant; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: C571130:CNR1 protein, human; D063387:Cannabinoid Receptor Antagonists; C543264:Cnr1 protein, rat; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D003094:Collagen; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3; D000077285:Rimonabant