Article

Effect of cannabinoid receptor-2 agonist AM1241 on platelet-derived growth factor expression in the liver tissue of mice with hepatic fibrosis

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Objective: To investigate the effect of cannabinoid receptor-2 (CB2) agonist AM1241 on the mRNA and protein expression of platelet-derived growth factor (PDGF) and collagen-III (Col-III) in the liver tissue of mice with experimental liver fibrosis induced by carbon tetrachloride (CCl(4)). Methods: Totally 38 8-week-old male C57BL/6J mice were randomly divided into control group, model group, 3 mg/kg CB2 receptor agonist (AM1241) group, and 9 mg/kg AM1241 group. All mice, except for the control group, were treated with 30% CCl(4) (three times a week, 5 ml/kg body weight, 16 weeks) to establish a liver fibrosis model. Meanwhile, 3 and 9 mg/kg AM1421 was intraperitoneally injected for daily intervention, respectively. The dosage was adjusted according to actual body weight. The same solvent was given in the control group. The serum level of aspartate aminotransferase (AST) was measured by serum enzyme digestion. The liver inflammation and fibrosis were observed by HE staining of tissue slices. The mRNA and protein expression of PDGF and Col-III in hepatic tissue was determined by real-time PCR and immunohistochemistry. Results: Compared with the control group, the mice in model group showed severe liver fibrosis, significantly elevated serum AST level (742 ± 300.8 U/L vs 118.1 ± 31.1 U/L, P < 0.05), and significantly increased mRNA and protein expression of PDGF and Col-III in liver tissue (P < 0.05). Compared with the model group, the mice in 3 mg/kg AM1241 group and 9 mg/kg AM1241 group had less severe liver fibrosis, and significantly reduced serum AST levels (116.6 ± 13.68 U/L vs 742 ± 300.8 U/L, P < 0.05; 113.8 ± 16.01 U/L vs 742 ± 300.8 U/L, P < 0.05) and mRNA and protein expression of PDGF and Col-III in liver tissue (P < 0.05). Conclusion: CB2 receptor agonist AM1241 can inhibit the mRNA and protein expression of PDGF in the liver tissue of mice with hepatic fibrosis, and reduce extracellular matrix synthesis.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Moreover, the activation of endogenous CB2 in hepatic fibroblasts can reduce experimental liver fibrosis [15], and CB2 can reduce the extent of liver damage in acute liver injury caused by ischemia-reperfusion or concanavalin [16,17]. Our previous study also showed that the CB2 agonist AM1241 can inhibit the proliferation of the HSC-T6 cell line cultured in vitro by protecting against oxidative stress and reducing the production of ECM [18]; in vivo, our previous experiments showed that the CB2 agonist AM1241 can ameliorate carbon tetrachloride (CCl 4 )-induced liver fibrosis in mice by mediating the expression of platelet-derived growth factor (PDGF), thereby inhibiting the activation of HSCs to prevent the progression of liver fibrosis [19]. Many of these experimental results indicated that the CB2 receptor has anti-fibrosis effects. ...
... In mice exposed to CCl 4 , CB2 antagonist is manifested by increased fibrosis, while CB2 prevents fibrosis [24]. Our previous results have demonstrated that cannabinoid receptor agonists can inhibit the activation of HSCs in vivo and in vitro, delaying the development of liver fibrosis [18,19], which is consistent with the above findings. In addition, in animal models, the loss of CB2 results in collagen deposition, steatosis, and increased inflammation [25]. ...
Article
Full-text available
BACKGROUND This study aimed to investigate the effect of deleting the cannabinoid receptor 2 (CB2) gene on the development of hepatic fibrosis induced by carbon tetrachloride (CCl₄) in mice via regulating inflammation. MATERIAL AND METHODS The DNA was extracted from the tails of mice to identify whether the cannabinoid receptor 2 gene was successfully knocked out. A liver fibrosis model was established by an intraperitoneal injection of CCl₄ into mice. Hepatic damage and hepatic fibrosis were evaluated by detecting serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and staining paraffin sections of liver tissue with hematoxylin-eosin (HE). The secretion and distribution of collagen in liver tissue were observed by Masson staining. Western blot analysis was performed to detect the expression of a-smooth muscle actin (alpha-SMA), transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor alpha-induced protein 3 (A20), phosphorylated nuclear factor-kB p65 (p-NF-kappaB p65), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) in liver tissue. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-6 and TNF-alpha mRNA in liver tissue. RESULTS Compared with the control mice, the mice with CB2 knockout that were exposed to CCl₄ exhibited increased liver damage, liver fibrosis, and upregulated alpha-SMA, TGF-ß1, A20, and p-NF-kappaB p65 protein levels. IL-6 and TNF-alpha protein levels and mRNA levels were upregulated. CONCLUSIONS The deletion of the CB2 gene promoted the activation of hepatic stellate cells in mice with liver fibrosis and aggravated liver fibrosis by up-regulating the protein expression of A20 and p-NF-kappaB p65 and inducing inflammatory response, potentially providing new insight into the treatment of liver fibrosis.
ResearchGate has not been able to resolve any references for this publication.