Haiyan Jin1, Shuji Terai, Isao Sakaida. 1. Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Japan.
Abstract
BACKGROUND: Hepatic stellate cells (HSCs) play a pivotal role in liver fibrogenesis. Here, we studied whether the iron chelator deferoxamine (DFO) affected cultured HSC activation and apoptosis. METHODS: The effect of DFO on HSCs was investigated using quiescent and activated stellate cells. RESULTS: Treatment with DFO inhibited HSC activation, resulting in the reduced expression of alpha-smooth muscle actin protein and type I procollagen, matrix metalloproteinase-2 and -9, and tissue inhibitors of metalloproteinase-1 and -2 mRNAs. DFO induced apoptosis of activated HSCs, which was associated with decreasing Bcl-2 expression and the release of cytochrome c from the mitochondria to the cytosol with enhanced caspase-3 activity. DFO also induced activated HSCs to express peroxisome proliferator-activated receptor gamma with the reaccumulation of intracellular lipids. CONCLUSIONS: The iron chelation of stellate cells inhibits their activation, causing them to become deactivated as well as to undergo apoptosis. These data suggest a potential role for an iron chelation treatment of liver fibrosis.
BACKGROUND: Hepatic stellate cells (HSCs) play a pivotal role in liver fibrogenesis. Here, we studied whether the iron chelator deferoxamine (DFO) affected cultured HSC activation and apoptosis. METHODS: The effect of DFO on HSCs was investigated using quiescent and activated stellate cells. RESULTS: Treatment with DFO inhibited HSC activation, resulting in the reduced expression of alpha-smooth muscle actin protein and type I procollagen, matrix metalloproteinase-2 and -9, and tissue inhibitors of metalloproteinase-1 and -2 mRNAs. DFO induced apoptosis of activated HSCs, which was associated with decreasing Bcl-2 expression and the release of cytochrome c from the mitochondria to the cytosol with enhanced caspase-3 activity. DFO also induced activated HSCs to express peroxisome proliferator-activated receptor gamma with the reaccumulation of intracellular lipids. CONCLUSIONS: The iron chelation of stellate cells inhibits their activation, causing them to become deactivated as well as to undergo apoptosis. These data suggest a potential role for an iron chelation treatment of liver fibrosis.
Authors: A E Kossakowska; D R Edwards; S S Lee; L S Urbanski; A L Stabbler; C L Zhang; B W Phillips; Y Zhang; S J Urbanski Journal: Am J Pathol Date: 1998-12 Impact factor: 4.307
Authors: Paolo Santambrogio; Benedetta Gaia Erba; Alessandro Campanella; Anna Cozzi; Vincenza Causarano; Laura Cremonesi; Anna Gallì; Matteo Giovanni Della Porta; Rosangela Invernizzi; Sonia Levi Journal: Haematologica Date: 2011-06-28 Impact factor: 9.941