Metallothionein (MT) gene therapy leads to resolution of liver fibrosis. This study investigated whether reversal of the phenotype of activated hepatic stellate cells (HSC) contributes to the fibrinolysis effect of MT. Human HSC LX-2 cells were activated, as indicated, by expression of α-smooth muscle actin (α-SMA) and collagen-I and depressed expression of collagenases. Transfection with a plasmid containing human MT-II gene in the activated HSCs effectively increased the protein level of MT, which was accompanied by the reduction of protein levels of α-SMA and collagen-I and the decrease in their mRNA levels. This study demonstrates that reversal of the phenotype of activated HSCs is likely involved in the resolution of liver fibrosis observed in MT gene therapy.
See article at J Pharmacol Exp Ther 2013, 346:48–53.
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