GENE-EXPRESSION OF NEUROTROPHINS AND THEIR RECEPTORS IN CULTURED RAT VASCULAR SMOOTH-MUSCLE CELLS

Most previous researches on neurotrophins including nerve growth facto r (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) have focused on the nervous system, because their receptors are widely distributed in neuronal tissues. Recently, however, the partic ipation of neurotrophins in inflammation and atherosclerosis has been proposed. Therefore, the gene expression of neurotrophins is now an ur gent issue is to be investigated in nonneuronal tissues. Here, we eval uated the gene expression of neurotrophins and their receptors in rat cultured vascular smooth muscle cells (VSMCs) by the reverse transcrip tase-polymerase chain reaction method, The transcripts of NGF, NT-3, a nd TrkC thigh-affinity receptor for NT-3), and two BDNF alternative sp liced transcript variants with exons 3 and 4 were clearly detected in VSMCs cultured under conventional culture conditions. The upregulation of mRNA levels for NGF, two BDNF variants with exons 1 and 2, low-aff inity neurotrophin receptor, and high-affinity receptors, TrkA (for NG F) and TrkB (for BDNF), was observed in response to the treatment with serum and phorbol-ester following the serum-starvation. In contrast, the expression of NT-3 and TrkC genes was downregulated under these co nditions. Go-expression of these factors and their receptors and the c haracteristic regulation of their gene transcriptions suggest that the se factors play crucial roles in the function of VSMCs through an auto crine mechanism. (C) 1998 Academic Press.