The GABAB Receptor Inhibits Activation of Hepatic Stellate Cells
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Background/Aims Angiotensin II (Ang II) plays an important role in the activation of hepatic stellate cells (HSCs). In this study it was found that expression of the GABAB receptor was elevated in HSCs treated with Ang II. We attempted to elucidate the mechanism of the GABAB receptor in HSCs activation. Methods First, the target gene (GABAB receptor) was screened by gene chip in HSCs treated with Ang II. Second, the biological function of the GABAB receptor was analyzed by MTT, cell-cycle assay, real-time PCR, and western blot. The methods of MTT and cell-cycle assay were used to evaluate the effect of the GABAB receptor on proliferation and DNA synthesis of HSCs. Expression of ECM, TGF-β1, and α-SMA was analyzed by real-time PCR and western blot. Results The GABAB receptor’s specific agonist CGP35348 inhibited the activation of HSCs, which could be partially reversed by the GABAB receptor’s antagonist. Conclusions Our in-vitro results demonstrated that the GABAB receptor could inhibit HSCs activation.
- Friedman SL. Liver fibrosis—from bench to bedside. J Hepatol. 2003;38(1):S38–S53. doi:10.1016/S0168-8278(02)00429-4. CrossRef
- Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005;209:18. (Review. Erratum in: J Clin Invest. 2005:115–1100).
- Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem. 2000;28:2247–2250. doi:10.1074/jbc.275.4.2247. CrossRef
- Wei HS, Li DG, Lu HM, et al. Effects of AT1 receptor antagonist, losartan, on rat hepatic fibrosis induced by CCl4. World J Gastroenterol. 2000;6:540–545.
- Wei HS, Lu HM, Li DG, et al. The expression of AT1 receptor on hepatic stellate cells in rat fibrosis induced by CCl4. Chin Med J. 2001;114:383–587.
- Paizis G, Cooper ME, Schembri JM. Up-regulation of components of the renin–angiotensin system in the bile duct-ligated rat liver. Gastroenterology. 2002;123:1667–1676. doi:10.1053/gast.2002.36561. CrossRef
- Yoshiji H, Noguchi R, Ikenaka Y. Renin–Angiotensin system inhibitors as therapeutic alternatives in the treatment of chronic liver diseases. Curr Med Chem. 2007;14:2749–2754. doi:10.2174/092986707782360169. CrossRef
- Herath CB, Warner FJ, Lubel JS. Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1–7) levels in experimental biliary fibrosis. J Hepatol. 2007;47:387–395. doi:10.1016/j.jhep.2007.03.008. CrossRef
- Yoshiji H, Kuriyama S, Fukui H. Blockade of renin–angiotensin system in antifibrotic therapy. J Gastroenterol Hepatol. 2007;22(1):S93–S95. doi:10.1111/j.1440-1746.2006.04663.x. CrossRef
- Warner FJ, Lubel JS, McCaughan GW. Liver fibrosis: a balance of ACEs? Clin Sci (Lond). 2007;113:109–118. doi:10.1042/CS20070026. CrossRef
- Bataller R, Gäbele E, Parsons CJ. Systemic infusion of angiotensin II exacerbates liver fibrosis in bile duct-ligated rats. Hepatology. 2005;41:1046–1055. doi:10.1002/hep.20665. CrossRef
- Bettler B, Kaupmann K, Mosbacher J, et al. Molecular structure and physiological functions of GABA(B) receptors. Physiol Rev. 2004;84:835–867. doi:10.1152/physrev.00036.2003. CrossRef
- Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005;115:209–218.
- Pinzani M. PDGF and signal transduction in hepatic stellate cells. Front Biosci. 2002;7:d1720–d1726. CrossRef
- Wada W, Kuwano H, Hasegawa Y, Kojima I. The dependence of transforming growth factor-beta-induced collagen production on autocrine factor activin A in hepatic stellate cells. Endocrinology. 2004;145:2753–2759. doi:10.1210/en.2003-1663. CrossRef
- Parramón M, González MP, Herrero MT, Oset-Gasque MJ. GABAB receptors increase intracellular calcium concentrations in chromaffin cells through two different pathways: their role in catecholamine secretion. J Neurosci Res. 1995;41:65–72. doi:10.1002/jnr.490410108. CrossRef
- Oide H, Tateyama M, Wang XE, et al. Activated stellate (Ito) cells possess voltage-activated calcium current. Biochim Biophys Acta. 1999;1418:158–164. doi:10.1016/S0005-2736(99)00018-8. CrossRef
- The GABAB Receptor Inhibits Activation of Hepatic Stellate Cells
Digestive Diseases and Sciences
Volume 55, Issue 2 , pp 261-267
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Hepatic stellate cell
- Liver fibrogenesis
- GABAB receptor
- Extracellular matrix
- Industry Sectors
- Author Affiliations
- 1. The Institute of Infectious Diseases, Beijing Ditan Hospital, Beijing, 100011, China
- 2. Clinical Medical College, Lanzhou University, Lanzhou, 730000, China
- 3. Shanxi Medical University, Shanxi, 030001, China