title: Angiotensin II stimulates the nuclear translocation of Smad2 and induces PAI-1 mRNA in rat hepatic stellate cells.
abstract: It has recently been reported that angiotensin II (ANGII) stimulates gene expression of transforming growth factor-beta1 (TGF-beta1) and is involved in hepatic fibrosis. This effect is thought to be caused through ANGII type 1 receptor (ATR1). However, a role of ANGII at the postreceptor levels of TGF-beta1 signaling has not been identified. To clarify the role of ANGII on hepatic fibrosis, we investigated the effect of ANGII on rat hepatic stellate cells (HSCs). HSCs were isolated from male Sprague-Dawley rats. TGF-beta1 and matrix protein gene expression in HSCs was assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) using SYBR Green I. The nuclear translocation of Smad2 in HSCs after 20 min ANGII stimulation was analyzed by Western blotting. ANGII was found to induce TGF-beta1 and matrix protein gene expression in HSCs. The nuclear translocation of Smad2 in HSCs was also induced by ANGII stimulation. These effects of ANGII were almost completely blocked by the ATR1 antagonist, CS-866. ANGII induces TGF-beta1 and matrix protein mRNA, and stimulates rapid nuclear translocation of Smad2 in rat HSCs through ATR1, which indicates that the ATR1 blockade represents a novel approach for the possible prevention of hepatic fibrosis.
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2, B5, Yamada-oka, Suita, 565-0871, Osaka, Japan
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kamada
authors.forename: Shinji
authors.initials: S
authors.lastname: Tamura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kiso
authors.forename: Koji
authors.initials: K
authors.lastname: Fukui
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Doi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ito
authors.forename: Yuki
authors.initials: Y
authors.lastname: Terui
authors.forename: Takafumi
authors.initials: T
authors.lastname: Saito
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Togashi
authors.forename: Sumio
authors.initials: S
authors.lastname: Kawata
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa