, Volume 42, Issue 6, pp 475-484
Date: 29 Jun 2007

The iron chelator deferoxamine causes activated hepatic stellate cells to become quiescent and to undergo apoptosis

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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 α-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 γ 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.