Suppression of CB1 Cannabinoid Receptor by Lentivirus Mediated Small Interfering RNA Ameliorates Hepatic Fibrosis in Rats

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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. © 2012 Chen et al.

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Chen, S. W., Wu, B. Y., Xu, S. P., Fan, K. X., Yan, L., Gong, Y., … Wu, D. H. (2012). Suppression of CB1 Cannabinoid Receptor by Lentivirus Mediated Small Interfering RNA Ameliorates Hepatic Fibrosis in Rats. PLoS ONE, 7(12). https://doi.org/10.1371/journal.pone.0050850

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