Research of neuregulin-1（Nrg1）for Promoting rePair after sPinal cord injury via activating Nrg1-ErbB recePtor signaling transduction in mice
YAO Wei-cheng1 JIANG Qiong1 HU Cheng-liang1 XU Jun-ping1 XIE Qing1 SHEN Hui-fan1 HE Jia-hui1 JING Yong-bin2 ZHAO Wei-jiang1▲
1.Center for Neuroscience，Medical College of Shantou University，Guangdong Province，Shantou 515041，China；
2.Department of Orthopedic Surgery，the Second Hospital Affiliated to Harbin Medical University，Heilongjiang Province，Harbin 150001，China
Abstract：Objective To study the effects of Neuregulin-1（Nrg1）on the expression of molecules associated with repair of spinal cord injury in mice and to preliminarily explore the related molecular mechanism. Methods Twelve 3-month-old C57BL/6 female mice were evenly divided into control group and Nrg1 group，and each group contained 6 mice.Mice were administrated with either DMSO solvent or Nrg1β diluted in DMSO by tail vein injection for 7 consecutive days after spinal cord injury.Tissues within the injury site were collected for performing western blot to measure the expression level of the molecules involved after 6 weeks of routine feeding.The differences between two groups were compared. Results Compared with the control group，the phosphorylation levels of Nrg1 receptors ErbB4 and Neu were significantly elevated in the Nrg1 group（P＜0.01）.The protein levels of pmTOR and Bcl-2 were also significantly increased by Nrg1 when compared with the control group（P＜0.05）and the levels of PTEN，GFAP and Bax were apparently decreased in the Nrg1 group. Conclusion The phosphorylation levels of Nrg1 receptors ErbB4 and Neu can be increased by exogenous Nrg1.The protein levels of regeneration-promoting molecules after spinal cord injury，including pmTOR and Bcl-2，are elevated，whereas those of the regeneration-inhibiting molecules，including PTEN，GFAP and Bax，are reduced by exogenous Nrg1.These effects may be achievedbytheactivationof Erk1/2signalingpathways.
Li GL，Brodin G，Farooque M，et al.Apoptosis and expression of Bcl-2 after compression trauma to rat spinal cord［J］.J Neuropathol Exp Neurol，1996，55（3）：280-289.
［2］
Zhao WJ，Ren SG.Endogenous neuregulin-1 expression in the anterior pituitary of female Wistar-Furth rats during the estrous cycle［J］.J Southern Med Univ，2011，31（6）：921-927.
Zhao WJ，Schachner M.Neuregulin 1 enhances cell adhesion molecule L1expression in human glioma cells and promotes their migration as a function of malignancy［J］.J Neuropathol Exp Neurol，2013，72（3）：244-255.
［5］
Hobbs SS，Coffing SL，Le AT，et al.Neuregulin isoforms exhibit distinct patterns of ErbB family receptor activation［J］. Oncogene，2002，21（55）：8442-8452.
［6］
Harrison PJ，Weinberger DR.Schizophrenia genes，gene expression and neuropathology：on the matter of their convergence［J］.Mol Psychiatry，2005，10（1）：40-68.
［7］
Liu Y，Yu Y，Schachner M，et al.Neuregulin 1-β regulates cell adhesion molecule L1expression in the cortex and hippocampus of mice［J］.Biochem Biophys Res Commun，2013，441（1）：7-12.
［9］
Buonanno A，Fischbach GD.Neuregulin and ErbB receptor signaling pathways in the nervous system［J］.Curr Opin Neurobiol，2001，11（3）：287-296.
［10］
Corfas G，Roy K，Buxbaum JD.Neuregulin 1-ErbB signaling and the molecular/cellular basis of schizophrenia［J］. Nat Neurosci，2004，7（6）：575-580.
［11］
Liu Z，Jiang H，Li H，et al.The effects of neuregulin-1B on neuronal phenotypes of primary cultured dorsal root ganglion neurons by activation of PI3K/Akt［J］.Neurosci Lett，2012，511（1）：52-57.
［16］
Stefansson H，Sigurdsson E，Steinthorsdottir V，etal.Neuregulin 1 and susceptibility to schizophrenia［J］.Am J Hum Genet，2002，71（4）：877-892.
京公网安备 11010502046607号