Marubuchi Shigeki, Okuda Tomohiro, Tagawa Kazuhiko, Enokido Yasushi, Horiuchi Daisuke, Shimokawa Reiko, Tamura Takuya, Qi Mei-Ling, Eishi Yoshinobu, Watabe Kazuhiko, Shibata Masao, Nakagawa Masaya, Okazawa Hitoshi
Department of Neuropathology, Medical Research Institute and 21st Century Center of Excellence Program for Brain Integration and Its Disorders, Tokyo Medical and Dental University, Tokyo, Japan.
J Neurochem. 2006 Oct;99(1):70-83. doi: 10.1111/j.1471-4159.2006.04021.x.
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.
肝癌衍生生长因子（HDGF）是一种与高迁移率族B1蛋白家族同源的核蛋白。已知它可从细胞中释放出来，并作为分裂细胞的营养因子发挥作用。在本研究中，在运动神经元变性小鼠模型——聚谷氨酰胺结合蛋白-1（PQBP-1）转基因小鼠中，HDGF在变性开始前就在脊髓运动神经元中增加。HDGF促进原代培养的脊髓运动神经元的神经突延伸和存活。HDGF抑制新生大鼠体内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的p53显著增加。在凝胶迁移率变动分析中，p53与HDGF基因上游的一个序列结合，并在氯霉素乙酰转移酶（CAT）分析中通过顺式元件促进基因表达。最后，我们发现PQBP-1转基因小鼠脑脊液中的HDGF增加。总体而言，我们的结果表明HDGF是运动神经元的一种新型营养因子，并表明它可能在PQBP-1转基因小鼠中对运动神经元变性起到保护作用。
