title: Epidermal growth factor attenuates blood-spinal cord barrier disruption via PI3K/Akt/Rac1 pathway after acute spinal cord injury.
abstract: After spinal cord injury (SCI), disruption of blood-spinal cord barrier (BSCB) elicits blood cell infiltration such as neutrophils and macrophages, contributing to permanent neurological disability. Previous studies show that epidermal growth factor (EGF) produces potent neuroprotective effects in SCI models. However, little is known that whether EGF contributes to the integrity of BSCB. The present study is performed to explore the mechanism of BSCB permeability changes which are induced by EGF treatment after SCI in rats. In this study, we demonstrate that EGF administration inhibits the disruption of BSCB permeability and improves the locomotor activity in SCI model rats. Inhibition of the PI3K/Akt pathways by a specific inhibitor, LY294002, suppresses EGF-induced Rac1 activation as well as tight junction (TJ) and adherens junction (AJ) expression. Furthermore, the protective effect of EGF on BSCB is related to the activation of Rac1 both in vivo and in vitro. Blockade of Rac1 activation with Rac1 siRNA downregulates EGF-induced TJ and AJ proteins expression in endothelial cells. Taken together, our results indicate that EGF treatment preserves BSCB integrity and improves functional recovery after SCI via PI3K-Akt-Rac1 signalling pathway.
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Zheng
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Libing
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Sipin
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Hongxue
authors.initials: H
authors.lastname: Shi
authors.affiliation: Emergency Department, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Daqing
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Wenzhou Medical University, Ningbo, Zhejiang, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wei
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Zhouguang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Huazi
authors.initials: H
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D005947:Glucose / Q000172:deficiency; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010100:Oxygen; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D059748:Proteolysis / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000097:blood* / Q000188:drug therapy*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D002867:Chromones; D004815:Epidermal Growth Factor; D005947:Glucose; D009025:Morpholines; D018696:Neuroprotective Agents; D010100:Oxygen; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D020830:rac1 GTP-Binding Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: PI3K/Akt; Rac1; blood-spinal cord barrier; epidermal growth factor; spinal cord injury