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Transforming growth factor α protects against Fas‐mediated liver apoptosis in mice
Author(s) -
Kanda Daisuke,
Takagi Hitoshi,
Toyoda Mitsuo,
Horiguchi Norio,
Nakajima Hiroaki,
Otsuka Toshiyuki,
Mori Masatomo
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02677-7
Subject(s) - apoptosis , fas ligand , fulminant hepatic failure , genetically modified mouse , in vivo , transforming growth factor , tgf alpha , transgene , biology , cancer research , growth factor , immunology , receptor , medicine , endocrinology , programmed cell death , transplantation , liver transplantation , biochemistry , gene , microbiology and biotechnology
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.