Inhibition of cell proliferation and induction of apoptosis by ExFABP gene targeting.
Ex-FABP, an extracellular fatty acid binding lipocalin, is physiologically expressed by differentiating chicken chondrocytes and myoblasts. Its expression is enhanced after cell treatment with inflammatory stimuli and repressed by anti-inflammatory agents, behaving as an acute phase protein. Chicken liver fragments in culture show enhanced protein expression after bacterial endotoxin treatment. To investigate the biological role of Ex-FABP, we stably transfected proliferating chondrocytes with an expression vector carrying antisense oriented Ex-FABP cDNA. We observed a dramatic loss of cell viability and a strong inhibition of cell proliferation and differentiation. When chondrocytes were transfected with the antisense oriented Ex-FABP cDNA we observed that Ex-FABP down-modulation increased apoptotic cell number. Myoblasts transfected with the same expression vector showed extensive cell death and impaired myotube formation. We suggest that Ex-FABP acts as a constitutive survival protein and that its expression and activation are fundamental to protect chondrocytes from cell death.
Di Marco
Eddi
E
Istituto Nazionale per la Ricerca sul Cancro, Centro Biotecnologie Avanzate, Genova, Italy. dimarco@cba.unige.it
Sessarego
Nadia
N
Zerega
Barbara
B
Cancedda
Ranieri
R
Cancedda
Fiorella Descalzi
FD
D000818:Animals; D017209:Apoptosis; D030161:Avian Proteins; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D016373:DNA, Antisense / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D018390:Gene Targeting; D054834:Lipocalins; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism
D030161:Avian Proteins; D002352:Carrier Proteins; C066299:Ch21 protein, chicken; D016373:DNA, Antisense; D018076:DNA, Complementary; D050556:Fatty Acid-Binding Proteins; D054834:Lipocalins; D008070:Lipopolysaccharides