Smooth muscle enriched long noncoding RNA (SMILR) regulates cell proliferation

Background: Phenotypic switching of vascular smooth muscle cells from a contractile to a synthetic state is implicated in diverse vascular pathologies, including atherogenesis, plaque stabilization, and neointimal hyperplasia. However, very little is known about the role of long noncoding RNA (lncRN...

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Autores: Ballantyne, Margaret D., Pinel, Karine, Dakin, Rachel, Vesey, Alex T., Diver, Louise, Mackenzie, Ruth, García López, Raquel, Welsh, Paul, Sattar, Naveed, Hamilton, Graham, Nikhil, Joshi, Dweck, Marc R., Miano, Joseph M., McBride, Martin W., Newby, David E., McDonald, Robert, A., Baker, Andrew H.
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/34039
Acceso en línea:https://hdl.handle.net/10902/34039
Access Level:acceso abierto
Palabra clave:Aterosclerosis
Cell proliferation
MicroRNAs
RNA
Untranslated
Plasma protein
Human
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spelling Smooth muscle enriched long noncoding RNA (SMILR) regulates cell proliferationBallantyne, Margaret D.Pinel, KarineDakin, RachelVesey, Alex T.Diver, LouiseMackenzie, RuthGarcía López, RaquelWelsh, PaulSattar, NaveedHamilton, GrahamNikhil, JoshiDweck, Marc R.Miano, Joseph M.McBride, Martin W.Newby, David E.McDonald, Robert, A.Baker, Andrew H.AterosclerosisCell proliferationMicroRNAsRNAUntranslatedPlasma proteinHumanBackground: Phenotypic switching of vascular smooth muscle cells from a contractile to a synthetic state is implicated in diverse vascular pathologies, including atherogenesis, plaque stabilization, and neointimal hyperplasia. However, very little is known about the role of long noncoding RNA (lncRNA) during this process. Here, we investigated a role for lncRNAs in vascular smooth muscle cell biology and pathology. Methods and Results: Using RNA sequencing, we identified >300 lncRNAs whose expression was altered in human saphenous vein vascular smooth muscle cells following stimulation with interleukin-1α and platelet-derived growth factor. We focused on a novel lncRNA (Ensembl: RP11-94A24.1), which we termed smooth muscle-induced lncRNA enhances replication (SMILR). Following stimulation, SMILR expression was increased in both the nucleus and cytoplasm, and was detected in conditioned media. Furthermore, knockdown of SMILR markedly reduced cell proliferation. Mechanistically, we noted that expression of genes proximal to SMILR was also altered by interleukin-1α/platelet-derived growth factor treatment, and HAS2 expression was reduced by SMILR knockdown. In human samples, we observed increased expression of SMILR in unstable atherosclerotic plaques and detected increased levels in plasma from patients with high plasma C-reactive protein. Conclusions: These results identify SMILR as a driver of vascular smooth muscle cell proliferation and suggest that modulation of SMILR may be a novel therapeutic strategy to reduce vascular pathologies.Sources of Funding: This work is supported by the British Heart Foundation (Program grant: RG/09/005/27915 and FS11/12/28673). Dr Ballantyne is supported by the British Heart Foundation PhD Studentship (FS/12/66/30003) and Dr Baker is supported by the British Heart Foundation Chair of Translational Cardiovascular Sciences (CH/11/2/28733). Clinical PET/CT studies and Dr Vesey were funded by the British Heart Foundation (PG/12/8/29371). Drs Dweck and Newby are supported by the British Heart Foundation (FS/14/78/31020 and CH/09/002). Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). The Wellcome Trust Clinical Research Facility and the Clinical Research Imaging Center are supported by NHS Research Scotland (NRS) through NHS Lothian. Acknowledgments: We thank N. Britton and G. Aitchison for technical assistance.American Heart AssociationUniversidad de Cantabria20162016-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttps://hdl.handle.net/10902/34039Circulation, 2016, 133(21), 2050-2065reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/340392026-06-02T12:39:31Z
dc.title.none.fl_str_mv Smooth muscle enriched long noncoding RNA (SMILR) regulates cell proliferation
title Smooth muscle enriched long noncoding RNA (SMILR) regulates cell proliferation
spellingShingle Smooth muscle enriched long noncoding RNA (SMILR) regulates cell proliferation
Ballantyne, Margaret D.
Aterosclerosis
Cell proliferation
MicroRNAs
RNA
Untranslated
Plasma protein
Human
title_short Smooth muscle enriched long noncoding RNA (SMILR) regulates cell proliferation
title_full Smooth muscle enriched long noncoding RNA (SMILR) regulates cell proliferation
title_fullStr Smooth muscle enriched long noncoding RNA (SMILR) regulates cell proliferation
title_full_unstemmed Smooth muscle enriched long noncoding RNA (SMILR) regulates cell proliferation
title_sort Smooth muscle enriched long noncoding RNA (SMILR) regulates cell proliferation
dc.creator.none.fl_str_mv Ballantyne, Margaret D.
Pinel, Karine
Dakin, Rachel
Vesey, Alex T.
Diver, Louise
Mackenzie, Ruth
García López, Raquel
Welsh, Paul
Sattar, Naveed
Hamilton, Graham
Nikhil, Joshi
Dweck, Marc R.
Miano, Joseph M.
McBride, Martin W.
Newby, David E.
McDonald, Robert, A.
Baker, Andrew H.
author Ballantyne, Margaret D.
author_facet Ballantyne, Margaret D.
Pinel, Karine
Dakin, Rachel
Vesey, Alex T.
Diver, Louise
Mackenzie, Ruth
García López, Raquel
Welsh, Paul
Sattar, Naveed
Hamilton, Graham
Nikhil, Joshi
Dweck, Marc R.
Miano, Joseph M.
McBride, Martin W.
Newby, David E.
McDonald, Robert, A.
Baker, Andrew H.
author_role author
author2 Pinel, Karine
Dakin, Rachel
Vesey, Alex T.
Diver, Louise
Mackenzie, Ruth
García López, Raquel
Welsh, Paul
Sattar, Naveed
Hamilton, Graham
Nikhil, Joshi
Dweck, Marc R.
Miano, Joseph M.
McBride, Martin W.
Newby, David E.
McDonald, Robert, A.
Baker, Andrew H.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad de Cantabria
dc.subject.none.fl_str_mv Aterosclerosis
Cell proliferation
MicroRNAs
RNA
Untranslated
Plasma protein
Human
topic Aterosclerosis
Cell proliferation
MicroRNAs
RNA
Untranslated
Plasma protein
Human
description Background: Phenotypic switching of vascular smooth muscle cells from a contractile to a synthetic state is implicated in diverse vascular pathologies, including atherogenesis, plaque stabilization, and neointimal hyperplasia. However, very little is known about the role of long noncoding RNA (lncRNA) during this process. Here, we investigated a role for lncRNAs in vascular smooth muscle cell biology and pathology. Methods and Results: Using RNA sequencing, we identified >300 lncRNAs whose expression was altered in human saphenous vein vascular smooth muscle cells following stimulation with interleukin-1α and platelet-derived growth factor. We focused on a novel lncRNA (Ensembl: RP11-94A24.1), which we termed smooth muscle-induced lncRNA enhances replication (SMILR). Following stimulation, SMILR expression was increased in both the nucleus and cytoplasm, and was detected in conditioned media. Furthermore, knockdown of SMILR markedly reduced cell proliferation. Mechanistically, we noted that expression of genes proximal to SMILR was also altered by interleukin-1α/platelet-derived growth factor treatment, and HAS2 expression was reduced by SMILR knockdown. In human samples, we observed increased expression of SMILR in unstable atherosclerotic plaques and detected increased levels in plasma from patients with high plasma C-reactive protein. Conclusions: These results identify SMILR as a driver of vascular smooth muscle cell proliferation and suggest that modulation of SMILR may be a novel therapeutic strategy to reduce vascular pathologies.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10902/34039
url https://hdl.handle.net/10902/34039
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Heart Association
publisher.none.fl_str_mv American Heart Association
dc.source.none.fl_str_mv Circulation, 2016, 133(21), 2050-2065
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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