title: Galanin receptor 2 mediates antifibrogenic effects of galanin on hepatic stellate cells.
abstract: Galanin is an endogenous factor involved in the negative regulation of the biological effects of leptin in bioenergetic metabolism. Leptin promotes fibrogenic effects in hepatic stellate cells (HSCs), however, little is known about the effects of galanin on HSCs. In the present study, the biological functions of galanin and its receptors (GalRs) in HSCs were investigated using cell culturein vitro. It was found that galanin and GalR3 mRNA are expressed in quiescent and activated HSCs. GalR2 expression was undetectable in quiescent HSCs but was markedly induced in activated HSCs. In the HSC-T6 cell line, which is an activated rat HSC cell line, treatment with 100 nmol/l galanin significantly inhibited cell proliferation. It also inhibited transforming growth factor (TGF)-β1 and α-smooth muscle actin (SMA) expression and upregulated peroxisome proliferator-activated receptor (PPAR)-γ expression. Following the knockdown of GalR2 by specific small interfering RNA, the activation of GalR3 by galanin does not influence these effects of galanin on HSCs. However, activation of GalR2 alone by galanin following the knockdown of GalR3 inhibits HSC proliferation and TGF-β1 and α-SMA expression, in addition to inducing PPAR-γ expression. These data suggest that galanin inhibits HSC activation and suppresses the profibrogenic features of these cells, and these effects might be mediated by GalR2. Thus, galanin is a potential endogenous factor in the inhibition of liver fibrosis.
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Lingnan
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Da
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830028, P.R. China.
authors.forename: Yongnian
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Leiming
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Yuanwen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Jiangao
authors.initials: J
authors.lastname: Fan
keywords: galanin; hepatic stellate cells; peroxisome proliferator-activated receptor-γ; receptor; transforming growth factor-β; α-smooth muscle actin