title: Endophilin-1 regulates blood-brain barrier permeability via EGFR-JNK signaling pathway.
abstract: Endophilin-1 (Endo1), a multifunctional protein, is essential for synaptic vesicle endocytosis. However, the role and mechanism of endophilin-1 in blood-brain barrier (BBB) function are still unclear. This study was performed to determine whether endophilin-1 regulated BBB permeability via the EGFR-JNK signaling pathway. In the present study, we found that endophilin-1 over-expression in human cerebral microvascular endothelial cell (hCMEC/D3) increased BBB permeability and meanwhile reduced the expression levels of epidermal growth factor receptor (EGFR), phosphorylated c-Jun N-terminal kinase (p-JNK). While endophilin-1 knockdown led to the contrary results. After JNK inhibitor SP600125 was administered to the endophilin-1 silenced hCMEC/D3 cells, the transendothelial electrical resistance (TEER) value was decreased and the permeability coefficient values to 4kDa and 40kDa FITC-dextran were increased. Results observed by Transmission electron microscopy (TEM) showed that tight junctions (TJs) were opened. Moreover, immunofluorescence and Western blot assays revealed the discontinuous distribution of TJ-associated proteins ZO-1, occludin on cell-cell boundaries and a significant decrease in protein expressing levels. Therefore, these results indicated that endophilin-1 positively regulated BBB permeability via the EGFR-JNK signaling pathway in hCMEC/D3 cells, which would provide an experimental basis for further research on endophilin-1 mediated the opening of BBB.
authors.affiliation: Department of Neurology, First Affiliated Hospital, China Medical University, Shenyang 110001, People׳s Republic of China; Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, People׳s Republic of China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, People׳s Republic of China; Department of Neurology, Hainan Provincial Nongken General Hospital, Haikou 570311, People׳s Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurology, First Affiliated Hospital, China Medical University, Shenyang 110001, People׳s Republic of China; Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, People׳s Republic of China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, People׳s Republic of China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, People׳s Republic of China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, People׳s Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, People׳s Republic of China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, People׳s Republic of China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Neurology, Hainan Provincial Nongken General Hospital, Haikou 570311, People׳s Republic of China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Su
authors.affiliation: Department of Neurology, Hainan Provincial Nongken General Hospital, Haikou 570311, People׳s Republic of China.
authors.forename: Chaosheng
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Department of Neurology, First Affiliated Hospital, China Medical University, Shenyang 110001, People׳s Republic of China. Electronic address: shangxl2012@126.com.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Shang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000648:ultrastructure; D002460:Cell Line; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D062793:Occludin / Q000378:metabolism; D010539:Permeability; D010766:Phosphorylation; D019108:Tight Junctions / Q000648:ultrastructure; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C568985:OCLN protein, human; D062793:Occludin; C107640:SH3GL2 protein, human; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C512478:EGFR protein, human; D066246:ErbB Receptors; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Blood–brain barrier; Endophilin-1; Epidermal growth factor receptor; Tight junction; c-Jun N-terminal kinase