Transforming growth factor α protects against Fas‐mediated liver apoptosis in mice

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Abstract
The Fas/Fas ligand interaction plays a crucial role in various liver diseases, and administration of agonistic anti‐Fas antibody to mice causes massive hepatic apoptosis and fulminant hepatic failure. Several growth factors have recently been found to function in preventing apoptosis. In this study, we demonstrated that overexpression of transforming growth factor α (TGFα) has a dramatic protective effect on Fas‐mediated hepatic apoptosis at the biochemical and histological levels. Moreover, 85.7% (six out of seven) of TGFα transgenic mice survived the lethal liver damage, whereas all wild‐type mice died. Expression of Bcl‐xL, an anti‐apoptotic protein, was greatly increased in the transgenic mice. Taken together, our findings suggest that TGFα protects against Fas‐mediated liver apoptosis in vivo and up‐regulation of Bcl‐xL may participate in protective effect of TGFα.