title: Lentiviral Vector-Mediated p27kip1Expression Facilitates Recovery After Spinal Cord Injury.
abstract: Traumatic spinal cord injury (SCI) causes tissue loss and associated neurological dysfunction attributable to both mechanical damage and secondary biochemical and physiological responses. Upregulation of cell cycle proteins occurs in both neurons and glia after SCI and may contribute to these changes. Increased cell cycle protein is associated with neuronal and oligodendroglial apoptosis, reactive astrogliosis, glial scar formation, and microglial activation. Here, using lentiviral vectors (LV), we induced the expression of the cyclin-dependent kinase (CDK) inhibitor p27kip1in the lesioned spinal cord of adult rat. Treatment with LV-p27kip1significantly reduced the expression of cell cycle proteins and improved functional recovery. In addition, p27kip1overexpression also reduced lesion volume, decreased astrocytic reactivity, attenuated microglial activation, reduced cell death, and improved the local microenvironment. We suggest that these effects reflect the ability of p27kip1to inhibit cell cycle pathways. Thus, the present study provides further support for the therapeutic potential of cell cycle inhibitors in the treatment of SCI.
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, 20 Xi-Si Road, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Min-Hao
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, 20 Xi-Si Road, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Xu
authors.affiliation: Basic Medical Research Centre, Medical School, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Cheng-Niu
authors.initials: CN
authors.lastname: Wang
authors.affiliation: Department of Medical Imaging, Medical School, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Yi-
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Duan
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, 20 Xi-Si Road, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Kan
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Ai-Guo
authors.initials: AG
authors.lastname: Shen
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, 20 Xi-Si Road, Nantong, 226001, Jiangsu, People's Republic of China. wangyouhua_nt@126.com.
authors.forename: You-Hua
authors.initials: YH
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D004789:Enzyme Activation; D005822:Genetic Vectors / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D016086:Lentivirus / Q000378:metabolism*; D008124:Locomotion; D008297:Male; D017628:Microglia / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D019076:Transgenes
chemical_list: D018836:Inflammation Mediators; D004676:Myelin Basic Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D053148:Caspase 3
keywords: Apoptosis; Cell cycle; Proliferation; Spinal cord injury; p27kip1