| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
Platelet-derived growth factor B-chain (PDGF-B) is a factor originally isolated as a mitogen mainly for mesenchymal cells and glial cells. We found that the PDGF-B and the receptors were widely expressed in the CNS,and hypothesized that PDGF-B could work as an improtant neuro-regulatory, neurotrophic factor and as a factor to facilitate wound healing in CNS.Recently, we identified two PDGF-B transcripts of 3.5kb and 2.6kb, which were regulated independently in rat brain. In the present study, we determined the complete sequence of rat PDGF-B mRNA.The 5'-untranslated region sequence (5'-UTS) of 1 kb was highly homologous to that of human. Due to the preserved GC rich sequences in 5'-UTS,we assumed that 5'-UTS of rat PDGF-B message should inhibit the translation as reported in human PDGF-B message. On the other hand, we found that the 2.6kb transcript was a form of the 3.5kb message truncated at the 5' end, and that the predominant 2.6kb mRNA commenced 15 nt upstream of the signal peptide by PCR cloning and the RNase protection assay. In contrast to the constitutive expression of 3.5kb mRNA,the expression of 2.6kb mRNA increased markedly in accordance with those stages of brain development at which we had previously demonstrated an increased immunoreactivity for PDGF-B in neurons. Accordingly, it was suggested that the truncation of 5' UTS contributed to the expression of PDGF-B protein in the CNS.Lack of translational inhibitory 5' UTS of PDGF-B transcript and resultant efficient its protein translation have been reported only in a few transformed cells and cultured umbilical vein endothelial cell. We further extended this knowledge to the developing rat brain, and suggested that the similar mechanism could operate widely in non-transformed tissue in vivo.
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