Reversal of liver fibrosis by the antagonism of endocannabinoid CB1 receptor in a rat model of CCl 4-induced advanced cirrhosis

Laboratory Investigation

Volumn 92, Issue 3, 2012, Pages 384-395

  Giannone, Ferdinando A ^a,b   Baldassarre, Maurizio ^a,b   Domenicali, Marco ^a,b   Zaccherini, Giacomo ^a   Trevisani, Franco ^a   Bernardi, Mauro ^a,b   Caraceni, Paolo ^a,b  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

CB1 receptor antagonism; cytokines; endocannabinoid system; fibrogenesis; inflammation; liver cirrhosis

Indexed keywords

ALPHA SMOOTH MUSCLE ACTIN; CANNABINOID 1 RECEPTOR; CANNABINOID 1 RECEPTOR ANTAGONIST; CANNABINOID 2 RECEPTOR; CARBON TETRACHLORIDE; ENDOCANNABINOID; HYDROXYPROLINE; LIVER ENZYME; RIMONABANT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CONTROLLED STUDY; DISEASE SEVERITY; DRUG EFFECT; DRUG EFFICACY; ENZYME ACTIVITY; EXPERIMENTAL MODEL; FIBROGENESIS; GENE EXPRESSION REGULATION; IMMUNOHISTOCHEMISTRY; INFLAMMATION; LIVER CIRRHOSIS; LIVER LEVEL; LIVER METABOLISM; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; REAL TIME POLYMERASE CHAIN REACTION; RECEPTOR UPREGULATION;

ANIMALS; CARBON TETRACHLORIDE; DISEASE MODELS, ANIMAL; DRUG EVALUATION, PRECLINICAL; EXTRACELLULAR MATRIX; HEPATIC STELLATE CELLS; LIVER CIRRHOSIS, EXPERIMENTAL; MALE; PIPERIDINES; PYRAZOLES; RATS; RATS, WISTAR; RECEPTOR, CANNABINOID, CB1; RECEPTOR, CANNABINOID, CB2; REMISSION INDUCTION;

EID: 84857762880     PISSN: 00236837     EISSN: 15300307     Source Type: Journal    
DOI: 10.1038/labinvest.2011.191     Document Type: Article

References (49)

1. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005;115:209-218. (Pubitemid 40385459)
2. Siegmund SV, Schwabe RF. Endocannabinoids and liver disease. II. Endocannabinoids in the pathogenesis and treatment of liver fibrosis. Am J Physiol Gastrointest Liver Physiol 2008;294:G357-G362. (Pubitemid 351253327)
3. Hézode C, Roudot-Thoraval F, Nguyen S, et al. Daily cannabis smoking as a risk factor for fibrosis progression in chronic hepatitis C. Hepatology 2005;42:63-71. (Pubitemid 40911312)
4. Teixeira-Clerc F, Julien B, Grenard P, et al. CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Nat Med 2006;12:671-676. (Pubitemid 43865236)
5. Julien B, Grenard P, Teixeira-Clerc F, et al. Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology 2005;128: 742-755. (Pubitemid 40585376)
6. De Petrocellis L, Di Marzo V. An introduction to the endocannabinoid system: from the early to the latest concepts. Best Pract Res Clin Endocrinol Metab 2009;23:1-15.
7. Caraceni P, Domenicali M, Giannone F, et al. The role of the endocannabinoid system in liver diseases. Best Pract Res Clin Endocrinol Metab 2009;23:65-77.
8. Domenicali M, Caraceni P, Giannone F, et al. Cannabinoid type 1 receptor antagonism delays ascites formation in rats with cirrhosis. Gastroenterology 2009;137:341-349.
9. Domenicali M, Caraceni P, Principe A, et al. A novel sodium overload test predicting ascites decompensation in rats with CCl4-induced cirrhosis. J Hepatol 2005;43:92-97. (Pubitemid 40805278)
10. Pacher P, Bátkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 2006;58:389-462. (Pubitemid 44394908)
11. Li C, Jones PM, Persaud SJ. Role of the endocannabinoid system in food intake, energy homeostasis and regulation of the endocrine pancreas. Pharmacol Ther 2011;129:307-320.
12. Jamall IS, Finelli VN, Que Hee SS. A simple method to determine nanogram levels of 4-hydroxyproline in biological tissues. Anal Biochem 1981;112:70-75.
13. Caraceni P, Pertosa AM, Giannone F, et al. Antagonism of the cannabinoid CB-1 receptor protects rat liver against ischaemiareperfusion injury complicated by endotoxaemia. Gut 2009;58: 1135-1143.
14. Kenneth J, Livak, Thomas D. Schmittgen. Analysis of relative gene expression data using real-time quantitative PCR and the 2-[Delta][Delta]CT method. Methods 2001;25:402-408.
15. Mandal M, Das S, Chakraborti T, et al. Role of matrix metalloprotease-2 in oxidant activation of Ca2 ATPase by hydrogen peroxide in pulmonary vascular smooth muscle plasma membrane. J Biosci 2003;28:205-213. (Pubitemid 36330522)
16. Iredale P.J. Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. J Clin Invest 2007;117:539-548.
17. Friedman SL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev 2008;88:125-172.
18. Siegmund SV, Qian T, De Minicis S, et al. The endocannabinoid 2-arachidonoyl glycerol induces death of hepatic stellate cells via mitochondrial reactive oxygen species. FASEB J 2007;21:2798-2806. (Pubitemid 47372747)
19. Siegmund SV, Uchinami H, Osawa Y, et al. Anandamide induces necrosis in primary hepatic stellate cells. Hepatology 2005;41:1085-1095. (Pubitemid 40593916)
20. Lowes KN, Brennan BA, Yeoh GC, et al. Oval cell numbers in human chronic liver diseases are directly related to disease severity. Am J Pathol 1999;154:537-541. (Pubitemid 29094103)
21. Richardson MM, Jonsson JR, Powell EE, et al. Progressive fibrosis in nonalcoholic steatohepatitis: association with altered regeneration and a ductular reaction. Gastroenterology 2007;133:80-90. (Pubitemid 47031146)
22. Pinzani M, Milani S, De FR, et al. Endothelin 1 is overexpressed in human cirrhotic liver and exerts multiple effects on activated hepatic stellate cells. Gastroenterology 1996;110:534-548. (Pubitemid 26043888)
23. Feng HQ, Weymouth ND, Rockey DC. Endothelin antagonism in portal hypertensive mice: implications for endothelin receptor-specific signaling in liver disease. Am J Physiol Gastrointest Liver Physiol 2009;297:G27-G33.
24. Aram G, Potter JJ, Liu X, et al. Lack of inducible nitric oxide synthase leads to increased hepatic apoptosis and decreased fibrosis in mice after chronic carbon tetrachloride administration. Hepatology 2008;47:2051-2058. (Pubitemid 351945571)
25. Asadullah K, Sterry W, Volk HD. Interleukin-10 therapy-review of a new approach. Pharmacol Rev 2003;55:241-269.
26. Grü tz G. New insights into the molecular mechanism of interleukin-10-mediated immunosuppression. J Leukoc Biol 2005;77:3-15. (Pubitemid 40310687)
27. Louis H, Van Laethem JL, Wu W, et al. Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon tetrachloride in mice. Hepatology 1998;28: 1607-1615. (Pubitemid 28549131)
28. Zhang LJ, Chen YX, Chen ZX, et al. Effect of interleukin-10 and plateletderived growth factor on expressions of matrix metalloproteinases-2 and tissue inhibitor of metalloproteinases-1 in rat fibrotic liver and cultured hepatic stellate cells. World J Gastroenterol 2004;10: 2574-2579.
29. Zhang LJ, Zheng WD, Shi MN, et al. Effects of interleukin-10 on activation and apoptosis of hepatic stellate cells in fibrotic rat liver. World J Gastroenterol 2006;12:1918-1923.
30. O'Sullivan LA, Liongue C, Lewis RS, et al. Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease. Mol Immunol 2007;44:2497-2506. (Pubitemid 46240311)
31. Mair M, Blaas L, sterreicher CH, et al. JAK-STAT signaling in hepatic fibrosis. Front Biosci 2011;17:2794-2811.
32. Ogata H, Chinen T, Yoshida T, et al. Loss of SOCS3 in the liver promotes fibrosis by enhancing STAT3-mediated TGF-beta1 production. Oncogene 2006;25:2520-2530.
33. Niwa Y, Kanda H, Shikauchi Y, et al. Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma. Oncogene 2005;24:6406-6417. (Pubitemid 41486474)
34. Arthur MJ. Fibrogenesis II. Metalloproteinases and their inhibitors in liver fibrosis. Am J Physiol Gastrointest Liver Physiol 2000;279: G245-G249.
35. Iredale JP, Benyon RC, Arthur MJ, et al. Tissue inhibitor of metalloproteinase-1 messenger RNA expression is enhanced relative to interstitial collagenase messenger RNA in experimental liver injury and fibrosis. Hepatology 1996;24:176-184. (Pubitemid 26249431)
36. Benyon RC, Iredale JP, Goddard S, et al. Expression of tissue inhibitor of metalloproteinases 1 and 2 is increased in fibrotic human liver. Gastroenterology 1996;110:821-831. (Pubitemid 26071850)
37. Zhou X, Hovell CJ, Pawley S, et al. Expression of matrix metalloproteinase-2 and-14 persists during early resolution of experimental liver fibrosis and might contribute to fibrolysis. Liver Int 2004;24:492-501. (Pubitemid 40484564)
38. Luo L, Zhou A. Antifibrotic activity of anisodamine in vivo is associated with changed intrahepatic levels of matrix metalloproteinase-2 and its inhibitor tissue inhibitors of metalloproteinases-2 and transforming growth factor beta1 in rats with carbon tetrachloride-induced liver injury. J Gastroenterol Hepatol 2009;24:1070-1076.
39. Xu GF, Li PT, Wang XY, et al. Dynamic changes in the expression of matrix metalloproteinases and their inhibitors, TIMPs, during hepatic fibrosis induced by alcohol in rats. World J Gastroenterol 2004;10:3621-3627.
40. Lin HC, Yang YY, Tsai TH, et al. The relationship between endotoxemia and hepatic endocannabinoids in cirrhotic rats with portal hypertension. J Hepatol 2011;54:1145-1153.
41. Murphy FR, Issa R, Zhou X, et al. Inhibition of apoptosis of activated hepatic stellate cells by tissue inhibitor of metalloproteinase-1 is mediated via effects on matrix metalloproteinase inhibition: implications for reversibility of liver fibrosis. J Biol Chem 2002;277:11069-11076. (Pubitemid 34952866)
42. Liu X, Hu H, Yin JQ. Therapeutic strategies against TGF-beta signalling pathway in hepatic fibrosis. Liver Int 2006;26:8-22.
43. D́az-Gil JJ, Garc?́a-Monzón C, Rúa C, et al. The anti-fibrotic effect of liver growth factor is associated with decreased intrahepatic levels of matrix metalloproteinases 2 and 9 and transforming growth factor beta 1 in bile duct-ligated rats. Histol Histopathol 2008;23:583-591. (Pubitemid 351552345)
44. Caraceni P, Viola A, Piscitelli F, et al. Circulating and hepatic endocannabinoids and endocannabinoid-related molecules in patients with cirrhosis. Liver Int 2010;30:816-825.
45. Munoz-Luque J, Ros J, Fernandez-Varo G, et al. Regression of fibrosis after chronic stimulation of cannabinoid CB2 receptor in cirrhotic rats. J Pharmacol Exp Ther 2008;324:475-483. (Pubitemid 351185849)
46. Patsenker E, Stoll M, Millonig G, et al. Cannabinoid receptor type I modulates alcohol-induced liver fibrosis. Mol Med 2011 (e-pub ahead of print).
47. Trebicka J, Racz I, Siegmund SV, et al. Role of cannabinoid receptors in alcoholic hepatic injury: steatosis and fibrogenesis are increased in CB2 receptor-deficient mice and decreased in CB1 receptor knockouts. Liver Int 2011;31:860-870.
48. Tam J, Liu J, Mukhopadhyay B, et al. Endocannabinoids in liver disease. Hepatology 2011;53:346-355.
49. Tam J, Vemuri VK, Liu J, et al. Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. J Clin Invest 2010;120:2953-2966.