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Analysis of the post-transcriptional control of platelet-derived growth factor expression in the brain.

大脑中血小板衍生生长因子表达的转录后控制分析。

基本信息

批准号：
08670246
负责人：
SASAHARA Masakiyo
金额：
$ 1.41万
依托单位：
Shiga University of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670246/
关键词：
Platelet-derived growth factor development brain mRNA cloning truncation neurotrophic factor 発現調節

项目摘要

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.

血小板源性生长因子B链（PDGF-B）是一种最初作为主要用于间充质细胞和神经胶质细胞的有丝分裂原分离的因子。我们发现PDGF-B及其受体在中枢神经系统中广泛表达，推测其可能是中枢神经系统中重要的神经调节因子、神经营养因子和促进创伤愈合的因子。本研究测定了大鼠PDGF-B mRNA的全序列，其中1 kb的5 '-非翻译区序列（5'-UTS）与人PDGF-B mRNA的5 '-UTS高度同源。由于在5 '-UTS中保留了富含GC的序列，我们假设大鼠PDGF-B信使的5'-UTS应该抑制人PDGF-B信使中报道的翻译。另一方面，通过PCR克隆和RNase保护实验，我们发现2.6kb的转录本是3.5kb的5'端截短的信使序列的一种形式，并且主要的2.6kb的mRNA起始于信号肽上游15 nt处。与3.5kbmRNA的组成型表达相反，2.6kbmRNA的表达显著增加，这与我们先前证明的神经元中PDGF-B免疫反应性增加的脑发育阶段一致。因此，5' UTS的截短有助于PDGF-B蛋白在中枢神经系统中的表达，只有少数转化细胞和培养的脐静脉内皮细胞中报道了PDGF-B转录本的翻译抑制性5' UTS的缺失及其导致的蛋白翻译效率。我们进一步将这一知识扩展到发育中的大鼠大脑，并提出类似的机制可以在体内非转化组织中广泛发挥作用。