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[Effects of anandamide on the activation and proliferation of hepatic stellate cells through cannabinoid-2 receptors].
Zhonghua Gan Zang Bing Za Zhi. 2008 Jun; 16(6):430-4.ZG

Abstract

OBJECTIVE

To study the effects of endogenous cannabinoid anandamide (AEA) and its putative endocannabinoid receptors (CBR) on the activation and proliferation of hepatic stellate cells (HSC) and to study the role played by AEA during liver fibrosis.

METHODS

By using immunofluorescence and cell culture, the expression of CBR 1 and 2 in the PDGF-stimulated HSCs was investigated. By using PCR and Western-blot, the effects of 10, 20mumol/L AEA and CBR2 antagonist AM630 on the cultured and activated HSC were observed. Methyl thiazolyl tetrazolium and flow cytometry were used to investigate whether AEA induces growth inhibition or apoptosis in the activated HSCs.

RESULTS

Both CBR1 and CBR2 receptors were detectable in cultured HSCs with a higher level of CBR2 than CBR1 (F = 116.797, P less than 0.01). When HSCs were stimulated by PDGF, the expression of CBR2 receptors was significantly enhanced (F = 7.878, P less than 0.05). HSC proliferation was dose-dependently inhibited by 10, 20, and 50micromol/L AEA, with the rates of 7.12%+/-0.34%, 12.52%+/-0.78%, 80.13%+/-1.57% respectively (F = 533.41, P less than 0.01). However, it did not induce apoptosis, but necrosis. The expressions of alpha-SMA, TGFb1, a1(I), a1(III) and TIMP-1 were significantly suppressed by 20micromol/L AEA, but CBR2 antagonist AM630 reversed this suppressor action of AEA.

CONCLUSIONS

AEA may inhibit activation and proliferation of HSCs; CBR2 receptors mediate AEA-induced inhibitory action on the activation of HSCs. This CBR2 receptor-mediated action and AEA on HSCs could be used as a therapeutic target against liver fibrosis.

Authors+Show Affiliations

Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

18578993

Citation

Liu, Hong-yan, et al. "[Effects of Anandamide On the Activation and Proliferation of Hepatic Stellate Cells Through Cannabinoid-2 Receptors]." Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology, vol. 16, no. 6, 2008, pp. 430-4.
Liu HY, Yang Q, Duan RX, et al. [Effects of anandamide on the activation and proliferation of hepatic stellate cells through cannabinoid-2 receptors]. Zhonghua Gan Zang Bing Za Zhi. 2008;16(6):430-4.
Liu, H. Y., Yang, Q., Duan, R. X., Zhang, Y. W., & Tang, W. X. (2008). [Effects of anandamide on the activation and proliferation of hepatic stellate cells through cannabinoid-2 receptors]. Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology, 16(6), 430-4.
Liu HY, et al. [Effects of Anandamide On the Activation and Proliferation of Hepatic Stellate Cells Through Cannabinoid-2 Receptors]. Zhonghua Gan Zang Bing Za Zhi. 2008;16(6):430-4. PubMed PMID: 18578993.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Effects of anandamide on the activation and proliferation of hepatic stellate cells through cannabinoid-2 receptors]. AU - Liu,Hong-yan, AU - Yang,Qiao, AU - Duan,Rui-xian, AU - Zhang,Yao-wen, AU - Tang,Wang-xian, PY - 2008/6/27/pubmed PY - 2010/8/11/medline PY - 2008/6/27/entrez SP - 430 EP - 4 JF - Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology JO - Zhonghua Gan Zang Bing Za Zhi VL - 16 IS - 6 N2 - OBJECTIVE: To study the effects of endogenous cannabinoid anandamide (AEA) and its putative endocannabinoid receptors (CBR) on the activation and proliferation of hepatic stellate cells (HSC) and to study the role played by AEA during liver fibrosis. METHODS: By using immunofluorescence and cell culture, the expression of CBR 1 and 2 in the PDGF-stimulated HSCs was investigated. By using PCR and Western-blot, the effects of 10, 20mumol/L AEA and CBR2 antagonist AM630 on the cultured and activated HSC were observed. Methyl thiazolyl tetrazolium and flow cytometry were used to investigate whether AEA induces growth inhibition or apoptosis in the activated HSCs. RESULTS: Both CBR1 and CBR2 receptors were detectable in cultured HSCs with a higher level of CBR2 than CBR1 (F = 116.797, P less than 0.01). When HSCs were stimulated by PDGF, the expression of CBR2 receptors was significantly enhanced (F = 7.878, P less than 0.05). HSC proliferation was dose-dependently inhibited by 10, 20, and 50micromol/L AEA, with the rates of 7.12%+/-0.34%, 12.52%+/-0.78%, 80.13%+/-1.57% respectively (F = 533.41, P less than 0.01). However, it did not induce apoptosis, but necrosis. The expressions of alpha-SMA, TGFb1, a1(I), a1(III) and TIMP-1 were significantly suppressed by 20micromol/L AEA, but CBR2 antagonist AM630 reversed this suppressor action of AEA. CONCLUSIONS: AEA may inhibit activation and proliferation of HSCs; CBR2 receptors mediate AEA-induced inhibitory action on the activation of HSCs. This CBR2 receptor-mediated action and AEA on HSCs could be used as a therapeutic target against liver fibrosis. SN - 1007-3418 UR - https://www.unboundmedicine.com/medline/citation/18578993/[Effects_of_anandamide_on_the_activation_and_proliferation_of_hepatic_stellate_cells_through_cannabinoid_2_receptors]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&issn=1007-3418&year=2008&vol=16&issue=6&fpage=430 DB - PRIME DP - Unbound Medicine ER -