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: Hitoshi Yoshiji, Shigeki Kuriyama, Ryuichi Noguchi, Yasuhide Ikenaka, Mitsuteru Kitade, Kosuke Kaji, Junichi Yoshii, Koji Yanase, Masaharu Yamazaki, Kiyoshi Asada, Tatsuhiro Tsujimoto, Takemi Akahane, Masahito Uemura, Hiroshi Fukui
• Journal: Hepatology research : the official journal of the Japan Society of Hepatology (Hepatol Res) Vol. 36 Issue 2 Pg. 124-9 (Oct 2006) ISSN: 1386-6346 [Print] Netherlands
• PMID: 16919500 (Publication Type: Journal Article)