Abstract
Background
It was well known that angiotension II can inhibit hepatic stellate cell activation. The GABAB receptor was upregulated when the hepatic stellate cell line was stimulated by angiotension II in our previous study. But the role of the GABAB receptor in liver fibrosis has never been reported.
Aim
In the present study, we investigated the effects of this receptor on carbon tetrachloride-induced liver fibrosis in rats.
Methods
The rats were divided into four groups including GABAB receptor agonist, antangonist, model and control group. α-smooth muscle actin (α-SMA) and GABAB receptor expression levels were detected by immunohistochemistry and real-time polymerase chain reaction. Liver function tests were performed once blood samples was taken; Western blot analysis was used to detect protein expression level of α-SMA and TGF-β1.
Results
We found baclofen ameliorated the CCl4-induced rats’s liver fibrosis. The highest liver enzymes and α-SMA protein levels were found in the CGP35348 group.
Conclusion
The GABAB receptor may have a protective role in the liver.
Similar content being viewed by others
References
Friedman SL. Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies. N Engl J Med. 1993;328:1828–1835.
Abdel-Aziz G, Lebeau G, Rescan PY, et al. Reversibility of hepatic fibrosis in experimentally induced cholestasis in rat. Am J Pathol. 1990;137:1333–1342.
Dufour JF, DeLellis R, Kaplan MM. Regression of hepatic fibrosis in hepatitis C with long-term interferon treatment. Dig Dis Sci. 1998;43:2573–2576.
Farci P, Roskams T, Chessa L, et al. Long-term benefit of interferon alpha therapy of chronic hepatitis D: regression of advanced hepatic fibrosis. Gastroenterology. 2004;126:1740–1749.
Rojkind M, Dunn MA. Hepatic fibrosis. Gastroenterology. 1979;76:849–863.
Iredale JP, Benyon RC, Pickering J, et al. Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J Clin Invest. 1998;102:538–549.
Lewis M, Howdle PD. The neurology of liver failure. QJM. 2003;96:623–633.
Jones EA, Weissenborn K. Neurology and the liver. J Neurol Neurosurg Psychiatry. 1997;63:279–293.
Albrecht J, Jones EA. Hepatic encephalopathy: molecular mechanisms underlying the clinical syndrome. J Neurol Sci. 1999;170:138–146.
Xiao F, Yu K, Dong F, Liang Y, Jun C, Wei H. The GABAB receptor inhibits activation of hepatic stellate cells. Dig Dis Sci. 2010;55:261–267.
Wang WW, Yang XS, Li X, et al. Changes in the expression of angiotensin II type 1 receptor in the development of liver fibrosis. Chin J Dig Dis. 2004;5:118–122.
Bettler B, Kaupmann K, Mosbacher J, Gassmann M. Molecular structure and physiological functions of GABA(B) receptors. Physiol Rev. 2004;84:835–867.
Castelli MP, Ingianni A, Stefanini E, Gessa GL. Distribution of GABA(B) receptor mRNAs in the rat brain and peripheral organs. Life Sci. 1999;64:1321–1328.
Isomoto S, Kaibara M, Sakurai-Yamashita Y, et al. Cloning and tissue distribution of novel splice variants of the rat GABAB receptor. Biochem Biophys Res Commun. 1998;253:10–15.
Schwarz DA, Barry G, Eliasof SD, Petroski RE, Conlon PJ, Maki RA. Characterization of gamma-aminobutyric acid receptor GABAB(1e), a GABAB(1) splice variant encoding a truncated receptor. J Biol Chem. 2000;275:32174–32181.
Wei K, Eubanks JH, Francis J, Jia Z, Snead OC 3rd. Cloning and tissue distribution of a novel isoform of the rat GABA(B)R1 receptor subunit. NeuroReport. 2001;12:833–837.
Tu H, Xu C, Zhang W, et al. GABAB receptor activation protects neurons from apoptosis via IGF-1 receptor transactivation. J Neurosci. 2010;30:749–759.
Biju MP, Pyroja S, Rajeshkumar NV, Paulose CS. Enhanced GABA(B) receptor in neoplastic rat liver: induction of DNA synthesis by baclofen in hepatocyte cultures. J Biochem Mol Biol Biophys. 2002;6:209–214.
Faroni A, Mantovani C, Shawcross SG, Motta M, Terenghi G, Magnaghi V. Schwann-like adult stem cells derived from bone marrow and adipose tissue express gamma-aminobutyric acid type B receptors. J Neurosci Res. 2011;89:1351–1362.
Velasco I, Tapia R. High extracellular gamma-aminobutyric acid protects cultured neurons against damage induced by the accumulation of endogenous extracellular glutamate. J Neurosci Res. 2002;67:406–410.
Kobuchi S, Tanaka R, Shintani T, et al. Mechanisms underlying the renoprotective effect of {gamma}-aminobutyric acid against the ischemia/reperfusion-induced renal injury in rats. J Pharmacol Exp Ther. 2011;338:767–774.
Zeisberg M, Yang C, Martino M, et al. Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem. 2007;282:23337–23347.
Acknowledgments
The study was supported by the National Natural Science Foundation of China (30800509).
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fan, W., Shi, B., Wei, H. et al. γ-Aminobutyric Acid B Receptor Improves Carbon Tetrachloride-Induced Liver Fibrosis in Rats. Dig Dis Sci 58, 1909–1915 (2013). https://doi.org/10.1007/s10620-013-2623-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-013-2623-z