Neuroprotective effect of sonic hedgehog up-regulated in Schwann cells following sciatic nerve injury.
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.
Hashimoto
Manabu
M
Department of Neurochemistry, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan.
Ishii
Kunihiro
K
Nakamura
Yasuko
Y
Watabe
Kazuhiko
K
Kohsaka
Shinichi
S
Akazawa
Chihiro
C
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism*; D020426:Sciatic Neuropathy / Q000473:pathology*; D013997:Time Factors; D014162:Transfection / Q000379:methods; D015854:Up-Regulation / Q000502:physiology*; D000071676:Zinc Finger Protein GLI1
D019208:Brain-Derived Neurotrophic Factor; C498521:Gli1 protein, rat; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D009418:S100 Proteins; D000071676:Zinc Finger Protein GLI1