title: Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood-Spinal Cord Barrier and Functional Recovery.
abstract: The blood-spinal cord barrier (BSCB) plays important roles in the recovery of spinal cord injury (SCI), and caveolin-1 is essential for the integrity and permeability of barriers. Basic fibroblast growth factor (bFGF) is an important neuroprotective protein and contributes to the survival of neuronal cells. This study was designed to investigate whether bFGF is beneficial for the maintenance of junction proteins and the integrity of the BSCB to identify the relations with caveolin-1 regulation. We examined the integrity of the BSCB with Evans blue dye and fluorescein isothiocyanate-dextran extravasation, measured the junction proteins and matrix metalloproteinases, and evaluated the locomotor function recovery. Our data indicated that bFGF treatment improved the recovery of BSCB and functional locomotion in contusive SCI model rats, reduced the expression and activation of matrix metalloproteinase-9, and increased the expressions of caveolin-1 and junction proteins, including occludin, claudin-5, p120-catenin, and β-catenin. In the brain, in microvascular endothelial cells, bFGF treatment increased the levels of junction proteins, caveolin-1 small interfering RNA abolished the protective effect of bFGF under oxygen-glucose deprivation conditions, and the expression of fibroblast growth factor receptor 1 and co-localization with caveolin-1 decreased significantly, which could not be reversed by bFGF treatment. These findings provide a novel mechanism underlying the beneficial effects of bFGF on the BSCB and recovery of SCI, especially the regulation of caveolin-1.
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Li-Bing
authors.initials: LB
authors.lastname: Ye
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Xi-Chong
authors.initials: XC
authors.lastname: Yu
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Qing-Hai
authors.initials: QH
authors.lastname: Xia
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Emergency Department, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Da-Qing
authors.initials: DQ
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Ningbo, Zhejiang, 315300, China.
authors.forename: Fenzan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Ningbo, Zhejiang, 315300, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Wei
authors.affiliation: Ningbo Medical Treatment Center, Li Huili Hospital, Ningbo, Zhejiang, 315000, China.
authors.forename: Xie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Zheng
authors.affiliation: Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Science, Chinese PLA General Hospital, Beijing, 100048, China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Fu
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Hua-Zi
authors.initials: HZ
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. xfxj2000@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. hyzhang@wmu.edu.cn.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects; D005070:Evans Blue / Q000493:pharmacokinetics; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008124:Locomotion / Q000187:drug effects; D055806:Microvessels / Q000166:cytology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: D051242:Caveolin 1; D034741:RNA, Small Interfering; D016222:Fibroblast Growth Factor 2; D005070:Evans Blue
keywords: BSCB; Caveolin-1; FGFR1; Junctions; bFGF