Hashimoto Manabu, Ishii Kunihiro, Nakamura Yasuko, Watabe Kazuhiko, Kohsaka Shinichi, Akazawa Chihiro
Department of Neurochemistry, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan.
J Neurochem. 2008 Nov;107(4):918-27. doi: 10.1111/j.1471-4159.2008.05666.x. Epub 2008 Sep 11.
The physiological roles of sonic hedgehog (Shh) have been intensively characterized in development of various organs. However, their functions in adult tissues have not been fully elucidated. We investigated the expression and the potential function of Shh in crush-injured adult rat sciatic nerves. The Shh expression was up-regulated in Schwann cells adjacent to the injured site. The time-course analyses of various neurotrophic factors revealed the up-regulation of Shh mRNA followed by that of brain-derived neurotrophic factor (BDNF) mRNA. The continuous administration of cyclopamine, a hedgehog signal inhibitor, to the injured site suppressed the increase of BDNF expression and deteriorated the survival of motor neurons in lumbar spinal cord. Treatment of exogenous Shh in cultured Schwann cells enhanced the BDNF expression. The BDNF promoter activity (exon I and II) was increased in IMS32 cells co-transfected with Shh and its receptor Smoothened. These findings imply that the up-regulated expression of Shh in Schwann cells may play an important role in injured motor neurons through the induction of BDNF.
音猬因子（Shh）的生理作用在各种器官的发育过程中已得到深入研究。然而，其在成体组织中的功能尚未完全阐明。我们研究了Shh在成年大鼠坐骨神经挤压损伤中的表达及潜在功能。在损伤部位附近的施万细胞中，Shh表达上调。对各种神经营养因子的时间进程分析显示，Shh mRNA上调后，脑源性神经营养因子（BDNF）mRNA也上调。向损伤部位持续给予环杷明（一种刺猬信号抑制剂）可抑制BDNF表达的增加，并使腰脊髓运动神经元的存活情况恶化。在培养的施万细胞中外源给予Shh可增强BDNF表达。在与Shh及其受体Smoothened共转染的IMS32细胞中，BDNF启动子活性（外显子I和II）增加。这些发现表明，施万细胞中Shh表达上调可能通过诱导BDNF在损伤的运动神经元中发挥重要作用。
