Hepatic expression of cannabinoid receptors CB1 and CB2 correlate with fibrogenesis in patients with chronic hepatitis B
- PMID: 28315398
- DOI: 10.1016/j.ijid.2017.03.008
Hepatic expression of cannabinoid receptors CB1 and CB2 correlate with fibrogenesis in patients with chronic hepatitis B
Abstract
Background: The endocannabinoid system is involved in the pathogenesis of liver fibrosis. However, most of the findings in this area have come from experimental studies in animal models or clinical trials on chronic hepatitis C. The roles of cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) in hepatofibrosis in patients with chronic hepatitis B (CHB) have not been studied fully. This study aimed to explore the relationship between liver fibrosis and the expression of CB1 and CB2 in patients with CHB.
Methods: Eighty liver biopsy specimens from patients with CHB (52 male, 28 female) were analyzed in this study. Fibrosis was staged on a scale of 1 to 4 (F1 to F4, with F4 defining cirrhosis). There were 20 samples for each fibrosis stage. The expression of hepatic alpha-smooth muscle actin (α-SMA), CB1, and CB2 was detected by immunohistochemistry.
Results: Hepatic CB1 and CB2 were expressed in all patients with CHB. The degree of fibrosis was significantly associated with the increased expression of CB1 and CB2 in CHB. Furthermore a significant increase in cells positive for both CB1 and CB2 was detected in stage 3 and stage 4 disease compared to stage 1 and stage 2 disease. There was a strong positive association between CB1 expression and α-SMA expression. Moreover, double immunofluorescence staining for CB1 and α-SMA demonstrated that activated hepatic stellate cells (HSCs) express CB1.
Conclusions: The hepatic expression of CB1 and CB2 plays an important role during the progression of fibrosis induced by CHB. Endogenous activation of CB1 receptors in patients with CHB enhances fibrogenesis by direct effect on activated HSCs.
Keywords: Cannabinoid receptor 1; Cannabinoid receptor 2; Chronic hepatitis B; Hepatic stellate cells; Liver fibrosis.
Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Similar articles
-
Antifibrogenic role of the cannabinoid receptor CB2 in the liver.Gastroenterology. 2005 Mar;128(3):742-55. doi: 10.1053/j.gastro.2004.12.050. Gastroenterology. 2005. PMID: 15765409
-
[The endocannabinoid system as a novel target for the treatment of liver fibrosis].Pathol Biol (Paris). 2008 Feb;56(1):36-8. doi: 10.1016/j.patbio.2007.01.001. Epub 2007 Apr 6. Pathol Biol (Paris). 2008. PMID: 17412522 Review. French.
-
CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis.Nat Med. 2006 Jun;12(6):671-6. doi: 10.1038/nm1421. Epub 2006 May 21. Nat Med. 2006. PMID: 16715087
-
Regression of fibrosis after chronic stimulation of cannabinoid CB2 receptor in cirrhotic rats.J Pharmacol Exp Ther. 2008 Feb;324(2):475-83. doi: 10.1124/jpet.107.131896. Epub 2007 Nov 20. J Pharmacol Exp Ther. 2008. PMID: 18029545 Free PMC article.
-
Role of cannabinoids in chronic liver diseases.World J Gastroenterol. 2008 Oct 28;14(40):6109-14. doi: 10.3748/wjg.14.6109. World J Gastroenterol. 2008. PMID: 18985799 Free PMC article. Review.
Cited by
-
Peripherally Restricted CB1 Receptor Inverse Agonist JD5037 Treatment Exacerbates Liver Injury in MDR2-Deficient Mice.Cells. 2024 Jun 25;13(13):1101. doi: 10.3390/cells13131101. Cells. 2024. PMID: 38994954 Free PMC article.
-
The association between preconception cannabis use and gestational diabetes mellitus: The Preconception Period Analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium.Paediatr Perinat Epidemiol. 2024 Jan;38(1):69-85. doi: 10.1111/ppe.13008. Epub 2023 Sep 26. Paediatr Perinat Epidemiol. 2024. PMID: 37751914
-
Cannabinoids and the Gastrointestinal Tract.Clin Gastroenterol Hepatol. 2023 Dec;21(13):3217-3229. doi: 10.1016/j.cgh.2023.07.031. Epub 2023 Sep 9. Clin Gastroenterol Hepatol. 2023. PMID: 37678488 Free PMC article. Review.
-
GPCRs and fibroblast heterogeneity in fibroblast-associated diseases.FASEB J. 2023 Aug;37(8):e23101. doi: 10.1096/fj.202301091. FASEB J. 2023. PMID: 37486603 Free PMC article. Review.
-
Controversies surrounding peripheral cannabinoid receptor 1 in fatty liver disease.J Clin Invest. 2021 Nov 15;131(22):e154147. doi: 10.1172/JCI154147. J Clin Invest. 2021. PMID: 34779413 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous