title: MicroRNA-155 Regulates ROS Production, NO Generation, Apoptosis and Multiple Functions of Human Brain Microvessel Endothelial Cells Under Physiological and Pathological Conditions.
abstract: The microRNA-155 (miR155) regulates various functions of cells. Dysfunction or injury of endothelial cells (ECs) plays an important role in the pathogenesis of various vascular diseases. In this study, we investigated the role and potential mechanisms of miR155 in human brain microvessel endothelial cells (HBMECs) under physiological and pathological conditions. We detected the effects of miR155 silencing on ROS production, NO generation, apoptosis and functions of HBMECs at basal and in response to oxidized low density lipoprotein (ox-LDL). Western blot and q-PCR were used for analyzing the gene expression of epidermal growth factor receptor (EGFR)/extracellular regulated protein kinases (ERK)/p38 mitogen-activated protein kinase (p38 MAPK), phosphatidylinositol-3-kinase (PI3K) and serine/threonine kinase(Akt), activated caspase-3, and intercellular adhesion molecule-1 (ICAM-1). Results showed that under both basal and challenge situations: (1) Silencing of miR155 decreased apoptosis and reactive oxygen species (ROS) production of HBMECs, whereas, promoted nitric oxide (NO) generation. (2) Silencing of miR155 increased the proliferation, migration, and tube formation ability of HBMECs, while decreased cell adhesion ability. (3) Gene expression analyses showed that EGFR/ERK/p38 MAPK and PI3K/Akt were increased and that activated caspase-3 and ICAM-1 mRNA were decreased after knockdown of miR155. In conclusion, knockdown of miR155 could modulate ROS production, NO generation, apoptosis and function of HBMECs via regulating diverse gene expression, such as caspase-3, ICAM-1 and EGFR/ERK/p38 MAPK and PI3K/Akt pathways.
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Qunwen
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, 45435.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: He
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Kexia
authors.initials: K
authors.lastname: Bi
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Yusen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.|Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, 45435.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Ma
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000096:biosynthesis; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008077:Lipoproteins, LDL / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis
chemical_list: D008077:Lipoproteins, LDL; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: CELL FUNCTION; HUMAN BRAIN MICROVESSEL ENDOTHELIAL CELLS; ISCHEMIC STROKE; OXIDATIVE STRESS; REGULATORY MECHANISM; miR155