EXPRESSION OF NEUROTROPHIN GENES IN HUMAN FIBROBLASTS - DIFFERENTIAL REGULATION OF THE BRAIN-DERIVED NEUROTROPHIC FACTOR GENE

Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) an d neurotrophin-3 (NT-3) are structurally related survival and differen tiation factors for distinct sets of peripheral and central neurons. W e previously reported that BDNF and NGF gene expression are differenti ally regulated in mouse L929 fibroblasts. Here we examine expression o f these three neurotrophins in human fibroblasts. Northern blots detec ted BDNF and NT-3 mRNAs in fibroblasts derived from lung (WI-38), calv arium and foreskin. WI-38 cells and foreskin fibroblasts expressed 1.6 kb as well as 4 kb BDNF mRNAs whereas only the smaller BDNF mRNA was detected in calvarium fibroblasts. NGF mRNA was present in foreskin an d calvarium but not lung fibroblasts. In WI-38 cells serum treatment i ncreased levels of BDNF mRNA within 2 hr. Cycloheximide did not inhibi t the increase. Treatment with 12-O-tetradecanoyl phorbol-13-acetate ( TPA) transiently suppressed BDNF mRNA. Treatment with both serum and T PA first stimulated and then transiently suppressed BDNF mRNA. TPA and /or serum did not significantly affect BDNF mRNA in calvarium fibrobla sts. These results show that human fibroblasts derived from different tissues express and regulate neurotrophin genes differentially.