title: Upregulation of eIF-5A1 in the paralyzed muscle after spinal cord transection associates with spontaneous hindlimb locomotor recovery in rats by upregulation of the ErbB, MAPK and neurotrophin signal pathways.
abstract: It is well known that trauma is frequently accompanied by spontaneous functional recovery after spinal cord injury (SCI), but the underlying mechanisms remain elusive. In this study, BBB scores showed a gradual return of locomotor functions after SCT. Proteomics analysis revealed 16 differential protein spots in the gastrocnemius muscle between SCT and normal rats. Of these differential proteins, eukaryotic translation initiation factor 5A1 (elf-5A1), a highly conserved molecule throughout eukaryotes, exhibited marked upregulation in the gastrocnemius muscle after SCT. To study the role of eIF-5A1 in the restoration of hindlimb locomotor functions following SCT, we used siRNA to downregulate the mRNA level of eIF-5A1. Compared with untreated SCT control rats, those subjected to eIF-5A1 knockdown exhibited impaired functional recovery. Moreover, gene expression microarrays and bioinformatic analysis showed high correlation between three main signal pathways (ErbB, MAPK and neurotrophin signal pathways) and eIF-5A1. These signal pathways regulate cell proliferation, differentiation and neurocyte growth. Consequently, eIF-5A1 played a pivotal role via these signal pathways in hindlimb locomotor functional recovery after SCT, which could pave the way for the development of a new strategy for the treatment of spinal cord injury in clinical trials.
authors.affiliation: Institute of Neurological Disease, The State Key Laboratory of Biotherapy and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Shang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Xin-Fu
authors.initials: XF
authors.lastname: Zhou
authors.forename: Cheng-Yun
authors.initials: CY
authors.lastname: Li
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D006614:Hindlimb / Q000502:physiology*; D020935:MAP Kinase Signaling System; D009068:Movement; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D018739:Oncogene Proteins v-erbB / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000378:metabolism*; D040901:Proteomics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D015854:Up-Regulation; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D009414:Nerve Growth Factors; D018739:Oncogene Proteins v-erbB; D010448:Peptide Initiation Factors; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A