GABAB Receptor Inhibits Activation of Hepatic Stellate Cells

• Published in: Digestive diseases and sciences Vol. 55; no. 2; pp. 261 - 267
• Main Authors: Xiao, Fan, Yu, Kangkang, Dong, Fang, Liang, Yunlei, Jun, Cheng, Wei, Hongshan
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.02.2010; Springer US; Springer; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biological and medical sciences; Blotting, Western; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Disease Progression; DNA - genetics; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; GABA Antagonists - pharmacology; GABA-B Receptor Agonists; Gastroenterology; Gene Expression; Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - metabolism; Hepatic Stellate Cells - pathology; Hepatology; Immunohistochemistry; Liver Cirrhosis - genetics; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; Male; Medicine; Medicine & Public Health; Oligonucleotide Array Sequence Analysis; Oncology; Organophosphorus Compounds - pharmacology; Original Article; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; Receptors, GABA-B - biosynthesis; Receptors, GABA-B - genetics; Transplant Surgery; Vertebrates: anatomy and physiology, studies on body, several organs or systems; GABA; Extracellular matrix; TGF-β1; Liver fibrogenesis; receptor; Hepatic stellate cell; Spider cell; Liver; Gastroenterology; Metabolic diseases; Activation
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-009-0743-2

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.