title: Angiotensin-II and vascular endothelial growth factor interaction plays an important role in rat liver fibrosis development.
abstract: Both angiotensin-II (AT-II) and vascular endothelial growth factor (VEGF) have been shown to play important roles in the progression of liver fibrosis. However, the interaction of AT-II with VEGF in the liver fibrosis has not been elucidated yet. The aim of the current study was to elucidate a possible association between these molecules, especially in conjunction with the hepatic stellate cells (HSC). The effect of AT-II type 1 receptor blocker (ARB) was assessed on several indices of choline-deficient l-amino acid-defined (CDAA)-induced liver fibrogenesis. This ARB significantly suppressed liver fibrosis development along with suppression of the VEGF expression and neovascularization in the liver. In the cultured activated HSC, AT-II induced VEGF in a dose- and time-dependent manner. ARB and LY333531, a protein kinase C (PKC) inhibitor, attenuated this augmentation. These results indicated that AT-II and VEGF interaction played an important role in liver fibrosis development, and that in the activated HSC, AT-II utilized type 1 receptor and PKC as an intracellular signaling pathway to induce VEGF.
authors.affiliation: Third Department of Internal Medicine, Nara Medical University, Shijo-cho 840, Kashihara, Nara 634-8522, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshiji
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kuriyama
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Noguchi
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Ikenaka
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Kitade
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kaji
authors.forename: Junichi
authors.initials: J
authors.lastname: Yoshii
authors.forename: Koji
authors.initials: K
authors.lastname: Yanase
authors.forename: Masaharu
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Asada
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Tsujimoto
authors.forename: Takemi
authors.initials: T
authors.lastname: Akahane
authors.forename: Masahito
authors.initials: M
authors.lastname: Uemura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukui