Neuroprotective effect of sonic hedgehog up-regulated in Schwann cells following sciatic nerve injury

被引：86

作者：

Hashimoto, Manabu ^{[1
]}

Ishii, Kunihiro ^{[2
]}

Nakamura, Yasuko ^{[1
]}

Watabe, Kazuhiko ^{[3
]}

Kohsaka, Shinichi ^{[1
]}

Akazawa, Chihiro ^{[1
,2
]}

机构：

[1] NCNP, Natl Inst Neurosci, Dept Neurochem, Kodaira, Tokyo 1878502, Japan

[2] Tokyo Med & Dent Univ, Grad Sch Hlth & Sci, Dept Biochem & Biophys, Tokyo, Japan

[3] Tokyo Metropolitan Inst Neurosci, Tokyo, Japan

来源：

JOURNAL OF NEUROCHEMISTRY | 2008年 / 107卷 / 04期

关键词：

brain-derived neurotrophic factor; nerve injury; real-time polymerase chain reaction; Schwann cells; sciatic nerve; sonic hedgehog;

D O I：

10.1111/j.1471-4159.2008.05666.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：918 / 927

页数：10

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