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

FEBS Letters

Mori, Masatomo¹  Takagi, Hitoshi¹  Toyoda, Mitsuo¹  Nakajima, Hiroaki¹  Otsuka, Toshiyuki¹  Horiguchi, Norio¹  Kanda, Daisuke¹ 

[1] The First Department of Internal Medicine, Gunma University School of Medicine, 3-39-15 Showa, Maebashi, Gunma 371-8511, Japan

关键词: Fas/APO-1/CD95;    Apoptosis;    Transforming growth factor α;    Bcl-xL;    TGFα;    transforming growth factor α;    EGF;    epidermal growth factor;    TNF;    tumor necrosis factor;    NGF;    nerve growth factor;    HGF;    hepatocyte growth factor;    ALT;    alanine aminotransferase;    TUNEL;    terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling;    PI3-k;    phosphatidylinositol 3′-kinase;   

DOI  :  10.1016/S0014-5793(02)02677-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown