Hepatoma-derived growth factor, a new trophic factor for motor neurons, is up-regulated in the spinal cord of PQBP-1 transgenic mice before onset of degeneration
Hepatoma-derived growth factor, a new trophic factor for motor neurons, is up-regulated in the spinal cord of PQBP-1 transgenic mice before onset of degeneration
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DOI：
10.1111/j.1471-4159.2006.04021.x
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发表时间：
2006-10-01
影响因子：
4.7
通讯作者：
Okazawa, Hitoshi
中科院分区：
文献类型：
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作者：
Marubuchi, Shigeki;Okuda, Tomohiro;Okazawa, Hitoshi
肝癌衍生生长因子(HDGF)是一种与高迁移率族B1家族蛋白同源的核蛋白。众所周知，它可以从细胞中释放出来，并作为细胞分裂的营养因子。在这项研究中，在运动神经元变性的小鼠模型中，在变性开始之前，多谷氨酰胺结合蛋白-1(PQBP-1)转基因小鼠的脊髓运动神经元中HDGF增加。HDGF可促进原代培养的脊髓运动神经元突起的生长和存活。HDGF可抑制新生大鼠面神经切断后运动神经元的细胞死亡。我们还发现转基因小鼠脊髓运动神经元中P53的表达显著增加。在凝胶迁移率改变实验中，p53与HDGF基因上游的一个序列结合，并在氯霉素乙酰转移(CAT)实验中通过顺式元件促进基因的表达。最后，我们发现PQBP-1转基因小鼠的脑脊液中HDGF含量增加。综上所述，我们的结果表明HDGF是一种新的运动神经元营养因子，并提示它可能对PQBP-1转基因小鼠的运动神经元变性起到保护作用。
Hepatoma-derived growth factor (HDGF) is a nuclear protein homologous to the high-mobility group B1 family of proteins. It is known to be released from cells and to act as a trophic factor for dividing cells. In this study HDGF was increased in spinal motor neurons of a mouse model of motor neuron degeneration, polyglutamine-tract-binding protein-1 (PQBP-1) transgenic mice, before onset of degeneration. HDGF promoted neurite extension and survival of spinal motor neurons in primary culture. HDGF repressed cell death of motor neurons after facial nerve section in newborn rats in vivo. We also found a significant increase in p53 in spinal motor neurons of the transgenic mice. p53 bound to a sequence in the upstream of the HDGF gene in a gel mobility shift assay, and promoted gene expression through the cis-element in chloramphenicol acetyl transfer (CAT) assay. Finally, we found that HDGF was increased in CSF of PQBP-1 transgenic mice. Collectively, our results show that HDGF is a novel trophic factor for motor neurons and suggest that it might play a protective role against motor neuron degeneration in PQBP-1 transgenic mice.