title: Suppression of CB1 cannabinoid receptor by lentivirus mediated small interfering RNA ameliorates hepatic fibrosis in rats.
abstract: It is recognized that endogenous cannabinoids, which signal through CB1 receptors in hepatic stellate cells (HSCs), exert a profibrotic effect on chronic liver diseases. In this study, we suppressed CB1 expression by lentivirus mediated small interfering RNA (CB1-RNAi-LV) and investigated its effect on hepatic fibrosis in vitro and in vivo. Our results demonstrated that CB1-RNAi-LV significantly inhibited CB1 expression, and suppressed proliferation and extracellular matrix production in HSCs. Furthermore, CB1-RNAi-LV ameliorated dimethylnitrosamine induced hepatic fibrosis markedly, which was associated with the decreased expression of mesenchymal cell markers smooth muscle α-actin, vimentin and snail, and the increased expression of epithelial cell marker E-cadherin. The mechanism lies on the blockage of Smad signaling transduction induced by transforming growth factor β1 and its receptor TGF-β RII. Our study firstly provides the evidence that CB1-RNAi-LV might ameliorate hepatic fibrosis through the reversal of epithelial-to-mesenchymal transition (EMT), while the CB1 antagonists AM251 had no effect on epithelial-mesenchymal transitions of HSCs. This suggests that CB1 is implicated in hepatic fibrosis and selective suppression of CB1 by small interfering RNA may present a powerful tool for hepatic fibrosis treatment.
authors.affiliation: Department of Gastroenterology, NanLou Clinic, General Hospital of PLA, Beijing, China.
authors.forename: Si-Wen
authors.initials: SW
authors.lastname: Chen
authors.forename: Ben-Yan
authors.initials: BY
authors.lastname: Wu
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Xu
authors.forename: Ke-Xing
authors.initials: KX
authors.lastname: Fan
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gong
authors.forename: Jun-Bao
authors.initials: JB
authors.lastname: Wen
authors.forename: Dao-Hong
authors.initials: DH
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D015820:Cadherins; D034741:RNA, Small Interfering; D043884:Receptor, Cannabinoid, CB1