Transforming growth factor alpha protects against Fas-mediated liver apoptosis in mice.
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 alpha (TGFalpha) has a dramatic protective effect on Fas-mediated hepatic apoptosis at the biochemical and histological levels. Moreover, 85.7% (six out of seven) of TGFalpha 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 TGFalpha protects against Fas-mediated liver apoptosis in vivo and up-regulation of Bcl-xL may participate in protective effect of TGFalpha.
Kanda
Daisuke
D
The First Department of Internal Medicine, Gunma University School of Medicine, 3-39-15 Showa, Maebashi, Gunma 371-8511, Japan.
Takagi
Hitoshi
H
Toyoda
Mitsuo
M
Horiguchi
Norio
N
Nakajima
Hiroaki
H
Otsuka
Toshiyuki
T
Mori
Masatomo
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D019610:Cytoprotection / Q000502:physiology; D006801:Humans; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015996:Survival Rate; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D019076:Transgenes; D051020:bcl-X Protein; D019014:fas Receptor / Q000276:immunology*
D000911:Antibodies, Monoclonal; C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D016211:Transforming Growth Factor alpha; D051020:bcl-X Protein; D019014:fas Receptor; D000410:Alanine Transaminase; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases