期刊
BRAIN RESEARCH
卷 1606, 期 -, 页码 44-53出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2015.02.032
关键词
Endophilin-1; Blood-brain barrier; Tight junction; Epidermal growth factor receptor; c-Jun N-terminal kinase
资金
- National Natural Science Foundation of China [81100243, 81171131, 81272564, 81272795, 81100893]
- Natural Science Foundation of Liaoning Province in China [L2013296]
- Liaoning Science and Technology Plan Projects [2011225020]
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 INK 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 4 kDa and 40 kDa 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. (C) 2015 Elsevier B.V. All rights reserved.
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