title: Silencing microRNA-143 protects the integrity of the blood-brain barrier: implications for methamphetamine abuse.
abstract: MicroRNA-143 (miR-143) plays a critical role in various cellular processes; however, the role of miR-143 in the maintenance of blood-brain barrier (BBB) integrity remains poorly defined. Silencing miR-143 in a genetic animal model or via an anti-miR-143 lentivirus prevented the BBB damage induced by methamphetamine. miR-143, which targets p53 unregulated modulator of apoptosis (PUMA), increased the permeability of human brain endothelial cells and concomitantly decreased the expression of tight junction proteins (TJPs). Silencing miR-143 increased the expression of TJPs and protected the BBB integrity against the effects of methamphetamine treatment. PUMA overexpression increased the TJP expression through a mechanism that involved the NF-κB and p53 transcription factor pathways. Mechanistically, methamphetamine mediated up-regulation of miR-143 via sigma-1 receptor with sequential activation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3' kinase (PI3K)/Akt and STAT3 pathways. These results indicated that silencing miR-143 could provide a novel therapeutic strategy for BBB damage-related vascular dysfunction.
authors: Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors: Ying
authors: Y
authors: Bai
authors: Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors: Yuan
authors: Y
authors: Zhang
authors: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, China.
authors: Jun
authors: J
authors: Hua
authors: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, Jiangsu, China.
authors: Xiangyu
authors: X
authors: Yang
authors: Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors: Xiaotian
authors: X
authors: Zhang
authors: Virosis Laboratory, Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, 5333 Xi An Road, Changchun, 130062, China.
authors: Ming
authors: M
authors: Duan
authors: Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors: Xinjian
authors: X
authors: Zhu
authors: Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, Homburg D-66421, Germany.
authors: Wenhui
authors: W
authors: Huang
authors: Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors: Jie
authors: J
authors: Chao
authors: Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
authors: Rongbin
authors: R
authors: Zhou
authors: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, China.
authors: Gang
authors: G
authors: Hu
authors: Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.|Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, Jiangsu, China.
authors: Honghong
authors: H
authors: Yao
mesh_terms: D019969:Amphetamine-Related Disorders / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D062725:Tight Junction Proteins / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; C532884:MIRN143 microRNA, mouse; D016328:NF-kappa B; C488588:PUMA protein, mouse; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D062725:Tight Junction Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D008694:Methamphetamine