title: MicroRNA-107 prevents amyloid-beta induced blood-brain barrier disruption and endothelial cell dysfunction by targeting Endophilin-1.
abstract: The disruption of blood-brain barrier (BBB) and endothelial cell dysfunction, associated with the cerebrovascular deposition of the amyloid-beta (Abeta) protein, have been characterized as the key pathological characteristics in Alzheimer's disease (AD). In various biologic processes of AD, researchers have proven that mircroRNAs (miRNAs) play critical roles. However, the role and function of miRNAs in the disruption of BBB of AD still remain unclear. Here, we found that mircroRNA-107 (miR-107) is endogenously expressed in human brain microvascular endothelial cells (ECs) of BBB model, while it is significantly down-regulated in ECs pre-incubated with Abeta. Abeta significantly impairs the integrity, increases the permeability of BBB, inhibits the viability of endothelial cells (ECs), and meanwhile down-regulates the expression of tight junction proteins ZO-1, Occludin and Claudin-5. Overexpression of miR-107 largely abrogated Abeta-induced disruption of BBB and endothelial cell dysfunction. Furthermore, overexpression of miR-107 also down-regulates endophilin-1, which is involved in the regulation of BBB permeability and the expression of ZO-1, Occludin, and Claudin-5. Both bioinformatics and luciferase reporter assays demonstrated that Endophilin-1 was a direct and functional downstream target of miR-107. In conclusion, our results indicate that overexpression of miR-107 is able to prevent Abeta-induced blood-brain barrier disruption and endothelial cell dysfunction by targeting endophilin-1.
authors.affiliation: Department of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China; Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China; Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Heng
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Meiqing
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Renjia
authors.initials: R
authors.lastname: Zhong
authors.affiliation: Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Siwei
authors.initials: S
authors.lastname: Bi
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China. Electronic address: shangxl2012@163.com.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Shang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001483:Base Sequence; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D062725:Tight Junction Proteins / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D016229:Amyloid beta-Peptides; C549045:MIRN107 microRNA, human; D035683:MicroRNAs; D062725:Tight Junction Proteins
keywords: Alzheimer's disease; Blood-brain barrier; Endophilin-1; Endothelial cell; MicroRNA-107