title: HIV-1 Tat C modulates expression of miRNA-101 to suppress VE-cadherin in human brain microvascular endothelial cells.
abstract: HIV-1 infection leads to the development of HIV-associated neurological disorders. The HIV-1 Tat protein has been reported to exert an adverse effect on blood-brain barrier integrity and permeability. Perturbation in permeability is mainly caused by disruptions in adherens junctions and tight junction proteins. We have identified HIV-1 Tat C-induced disruption of VE-cadherin mediated by miRNA-101 in human brain microvascular endothelial cells (BMVECs). HIV-1 Tat C increased the expression of miR-101, which led to downregulation of VE-cadherin. Overexpression of miR-101 resulted into the suppression of VE-cadherin. Inhibition of miR-101 by the miRNA inhibitor enhanced the expression of VE-cadherin. We have demonstrated that VE-cadherin is a direct target of miR-101 using a luciferase reporter assay, which showed that mutated VE-cadherin 3'UTR and miR-101 cotransfection did not change luciferase activity. By overexpression and knockdown of miR-101, we have demonstrated that the expression level of claudin-5 is governed by the expression of VE-cadherin. These findings demonstrate a novel mechanism for the regulation of barrier permeability by miR-101 via posttranscriptional regulation of VE-cadherin in human BMVECs exposed to the HIV-1 Tat C protein.
authors.affiliation: Laboratory of Neurovirology and Inflammation Biology, Council of Scientific and Industrial Research-Centre for Cellular and Molecular Biology, Hyderabad-500007, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Mishra
authors.forename: Sunit Kumar
authors.initials: SK
authors.lastname: Singh
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D001921:Brain / Q000033:anatomy & histology; D015820:Cadherins / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D062507:Claudin-5 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D055806:Microvessels / Q000166:cytology; D008954:Models, Biological; D016601:RNA-Binding Proteins / Q000378:metabolism; D014162:Transfection; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000494:pharmacology*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D062507:Claudin-5; D049452:Green Fluorescent Proteins; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D062826:Zonula Occludens-1 Protein; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099152:Cadherin 5; C107466:CLDN5 protein, human; C534072:MIRN101 microRNA, human; C569042:TJP1 protein, human
references.citation: Am J Physiol Cell Physiol. 2004 May;286(5):C987-97
references.pmid: 15075197
references.citation: Nat Cell Biol. 2008 Aug;10(8):883-5
references.pmid: 18670447
references.citation: Trends Microbiol. 2012 Jun;20(6):282-90
references.pmid: 22564250
references.citation: J Cell Physiol. 2008 Sep;216(3):764-70
references.pmid: 18381601
references.citation: J Gen Virol. 2008 Mar;89(Pt 3):642-652
references.pmid: 18272754
references.citation: Nat Cell Biol. 2008 Aug;10(8):923-34
references.pmid: 18604199
references.citation: J Cell Physiol. 2013 May;228(5):1070-5
references.pmid: 23042033
references.citation: J Neuroinflammation. 2012 Jun 18;9:131
references.pmid: 22709905
references.citation: Blood. 2004 Mar 15;103(6):2205-13
references.pmid: 14630801
references.citation: J Cell Biol. 1967 Jul;34(1):207-17
references.pmid: 6033532
references.citation: J Cell Biol. 2003 May 12;161(3):653-60
references.pmid: 12743111
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13830-5
references.pmid: 20643939
references.citation: J Neurochem. 2012 Jul;122(2):382-91
references.pmid: 22524563
references.citation: J Biol Chem. 2011 Nov 25;286(47):41125-34
references.pmid: 21956116
references.citation: EMBO J. 2009 Mar 18;28(6):697-710
references.pmid: 19197241
references.citation: Brain Res. 2007 Dec 12;1184:333-44
references.pmid: 17976544
references.citation: J Cell Sci. 2008 Jul 1;121(Pt 13):2115-22
references.pmid: 18565824
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11466-71
references.pmid: 11027346
references.citation: Curr Opin Cell Biol. 2010 Oct;22(5):651-8
references.pmid: 20708398
references.citation: Nat Rev Immunol. 2005 Jan;5(1):69-81
references.pmid: 15630430
references.citation: Exp Cell Res. 1999 Oct 10;252(1):13-9
references.pmid: 10502395
references.citation: Curr Opin Hematol. 2012 May;19(3):218-23
references.pmid: 22395663
references.citation: Nat Rev Mol Cell Biol. 2004 Apr;5(4):261-70
references.pmid: 15071551
references.citation: J Cell Biol. 1992 Sep;118(6):1511-22
references.pmid: 1522121
references.citation: Cell. 1988 Dec 23;55(6):1189-93
references.pmid: 2849510
references.citation: Arterioscler Thromb Vasc Biol. 1999 Oct;19(10):2286-97
references.pmid: 10521356
references.citation: Nature. 1995 Jun 8;375(6531):497-500
references.pmid: 7539892
references.citation: Curr Opin Infect Dis. 2006 Feb;19(1):1-7
references.pmid: 16374210
references.citation: AIDS Res Hum Retroviruses. 2009 Mar;25(3):329-35
references.pmid: 19327051
references.citation: J Neurovirol. 2010 Jul;16(4):294-305
references.pmid: 20624003
references.citation: J Neurosci. 2008 Jul 30;28(31):7788-96
references.pmid: 18667611
references.citation: Nature. 2012 Dec 13;492(7428):252-5
references.pmid: 23143332
references.citation: Blood. 2006 Jun 15;107(12):4770-80
references.pmid: 16478881
references.citation: Inflammation. 2000 Apr;24(2):99-113
references.pmid: 10718113
references.citation: Virulence. 2012 Mar-Apr;3(2):222-9
references.pmid: 22460635
references.citation: Methods Mol Biol. 2006;342:101-13
references.pmid: 16957370
references.citation: AIDS Res Hum Retroviruses. 2009 Jul;25(7):691-9
references.pmid: 19621989
references.citation: Brain Res. 2011 Jul 5;1399:96-115
references.pmid: 21641584
references.citation: HIV AIDS (Auckl). 2010;2:39-49
references.pmid: 22096383
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: J Cereb Blood Flow Metab. 2005 Sep;25(9):1159-70
references.pmid: 15815581
references.citation: J Biol Chem. 2010 Jun 11;285(24):18319-25
references.pmid: 20378550
references.citation: Methods Mol Biol. 2011;762:355-70
references.pmid: 21717370
references.citation: J Clin Immunol. 2008 Sep;28(5):528-41
references.pmid: 18574677
references.citation: Brain Res. 2012 Feb 3;1436:13-9
references.pmid: 22197032
references.citation: Top Antivir Med. 2011 May-Jun;19(2):48-57
references.pmid: 21868822