title: Endoplasmic reticulum protein 29 protects cortical neurons from apoptosis and promoting corticospinal tract regeneration to improve neural behavior via caspase and Erk signal in rats with spinal cord transection.
abstract: Following spinal cord injury (SCI), limit spontaneous functional recovery often emerged. However, the neuronal mechanisms associated with this phenomenon still remains obscure. By using proteomics analysis, endoplasmic reticulum protein 29 (ERp29) was discovered to increase in the motor cortexes of spinal cord transection (SCT) rats for 28 days post-operation (dpo) compared with in 14dpo. Then, the change in the expression of ERp29 was confirmed by using reverse transcription polymerase chain reaction (RT-PCR) and Western blot. To determine the role of ERp29 in the recovery of locomotor functions following SCT, lentiviral vectors were used to up- and downregulate the expression level of ERp29. Here, we found that cortical neurons in vitro with high level of ERp29 expression exhibited a significant proliferation, characterized by smaller size of soma and more extensive axon outgrowth, compared with neurons used as control, while ERp29 silence got the opposite results. In vivo, Lentivirus was inject into the cerebral cortex following SCT at thoracic level 10, which resulted in an increase number of neuronal nuclei(NeuN)-positive cells and less apoptotic cells. Moreover, increased PKC-γ immunoreactivity density was also found in the spinal cord T9 level compared with control rats. This was associated with a great functional improvement, indicated by Basso, Beattie, Bresnahan (BBB) locomotor rating scale. Lastly, we verified that ERp29 acts as a regulator by regulating a group of genes related with cell survival and apoptosis, involving in caspase and Erk, but not PI3K. Our findings showed that ERp29 can improve locomotor function by promoting neuronal survival and axonal regeneration in SCT rats via caspase and Erk signal pathway.
authors.affiliation: Department of Anesthesiology and Institute of Neurological Disease, State Key Lab of Biotherapy, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Su-Juan
authors.initials: SJ
authors.lastname: Liu
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Mu
authors.initials: M
authors.lastname: He
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Qing-Jie
authors.initials: QJ
authors.lastname: Xia
authors.forename: Cheng-Yun
authors.initials: CY
authors.lastname: Li
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D011712:Pyramidal Tracts / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology
chemical_list: C110909:Erp29 protein, rat; D006360:Heat-Shock Proteins; D020169:Caspases