title: Vesicle miR-195 derived from Endothelial Cells Inhibits Expression of Serotonin Transporter in Vessel Smooth Muscle Cells.
abstract: Serotonin or 5-hydroxytryptamine (5-HT) has been shown to be essential in lots of physiological and pathological processes. It is well known that 5-HT and 5-HT transporter (5-HTT) play important roles in the pulmonary artery in pulmonary hypertension. However, little is known about the function of 5-HTT in other arteries. In this study we found that the expression of 5-HTT was elevated in injured carotid arteries and over-expression of 5-HTT induced proliferation of smooth muscle cells (SMCs); however, this phenotype could be reversed by knocking-down of 5-HTT or endothelial cells conditional medium (EC-CM). A 5-HTT inhibitor, fluoxetine, treated animals also exhibited reduced restenosis after injury. We identified that miR-195 was packaged in the extracellular vesicles from EC-CM. We further confirmed that extracellular vesicles could transfer miR-195 from ECs to SMCs to inhibit the expression of 5-HTT in SMCs and the proliferation of SMCs. These results provide the first evidence that ECs communicate with SMCs via micro-RNA195 in the regulation of the proliferation of SMCs through 5-HTT, which will contribute to a better understanding of communications between ECs and SMCs via micro-RNA. Our findings suggest a potential target for the control of vessel restenosis.
authors.affiliation: Molecular Pharmacology Laboratory, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Junzhong
authors.initials: J
authors.lastname: Gu
authors.affiliation: Molecular Pharmacology Laboratory, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiopulmonary Bypass, Cardiovascular Institute and Fuwai Hospital, PUMC &CAMS, Beijing, China.
authors.forename: Bingyang
authors.initials: B
authors.lastname: Ji
authors.affiliation: Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Department of Urology, Peking University Third Hospital, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Suzhou University, Suzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Tianjin Neurological Institute, Tianjin 300052, China.|Key Laboratory of Post-Neuroinjury Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China.
authors.forename: Rongcai
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, 2nd affiliated hospital of Harbin Medical University, Harbin, China.
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Cambridge Institute for Medical Research, Cambridge, UK.|Department of Haematology, University of Cambridge, Cambridge, UK.|Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK.
authors.forename: Shengjiang
authors.initials: S
authors.lastname: Tan
authors.affiliation: Aston Medical School, Aston University, Birmingham, UK.
authors.forename: Asif
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Molecular Pharmacology Laboratory, Institute of Molecular Medicine, Peking University, Beijing, China.|Novolife Translational and Regenerative Medicine Centre, Aston Medical School, Aston University, Birmingham, UK.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000818:Animals; D001692:Biological Transport; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism*; D000067128:Extracellular Vesicles / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D058426:Neointima / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: D017077:Culture Media, Conditioned; C552722:MIRN195 microRNA, human; D035683:MicroRNAs; D050486:Serotonin Plasma Membrane Transport Proteins