Inhibition of cell proliferation and induction of apoptosis by ExFABP gene targeting

• Published in: Journal of cellular physiology Vol. 196; no. 3; pp. 464 - 473
• Main Authors: Di Marco, Eddi, Sessarego, Nadia, Zerega, Barbara, Cancedda, Ranieri, Descalzi Cancedda, Fiorella
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2003
• Subjects: Animals; Apoptosis; Avian Proteins; Carrier Proteins - antagonists & inhibitors; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Differentiation; Cell Division; Cell Survival; Chick Embryo; Chondrocytes - cytology; Chondrocytes - metabolism; DNA, Antisense - genetics; DNA, Antisense - metabolism; DNA, Complementary - genetics; DNA, Complementary - metabolism; Fatty Acid-Binding Proteins; Gene Expression Regulation - drug effects; Gene Targeting; Lipocalins; Lipopolysaccharides - pharmacology; Liver - drug effects; Liver - metabolism; Myoblasts - cytology; Myoblasts - metabolism
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.10310

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. J. Cell. Physiol. 196: 464–473, 2003. © 2003 Wiley‐Liss, Inc.