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Dig Dis Sci (2010) 55:261267 DOI 10.1007/s10620-009-0743-2
ORIGINAL ARTICLE
The GABAB Receptor Inhibits Activation of Hepatic Stellate Cells
Fan Xiao Kangkang Yu Fang Dong Yunlei Liang Cheng Jun Hongshan Wei
Received: 15 October 2008 / Accepted: 27 January 2009 / Published online: 20 February 2009 Springer Science+Business Media, LLC 2009
Abstract 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-b1, and a-SMA was analyzed by real-time PCR and western blot. Results The GABAB receptors specic agonist CGP35348 inhibited the activation of HSCs, which could be partially reversed by the GABAB receptors antagonist. Conclusions
Our in-vitro results demonstrated that the GABAB receptor could inhibit HSCs activation.
Keywords Hepatic stellate cell Liver brogenesis
GABAB receptor Extracellular matrix TGF-b1
Introduction
Liver brosis results from chronic injury to the liver with accumulation of ECM protein. The accumulation of ECM protein destroys the hepatic architecture by forming a brous scar. Liver brosis is reversible, whereas cirrhosis, the end-stage consequence of brosis, is usually irreversible [1, 2]. Therefore, efforts to identify therapeutic targets to reverse or slow the progression of liver brosis focus on understanding brosis mechanisms.
The hepatic stellate cell (HSC) is the key brogenic cell. In the normal liver, HSCs reside in the space of Disse and are the major storage sites of vitamin A. Following chronic injury, HSCs are activated, changing from quiescent cells into proliferative, brogenic, and contractile myobro-blasts. This is characterized by progressive changes in ECM, cellular composition, and function. Some proliferative cytokines, for example platelet-derived growth factors (PDGF), and brogenetic cytokines such as transforming growth factor-beta1 (TGF-b1), are the major cytokines involved in the process of activation of...