Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1

Autores
Caon, Ilaria; Bartolini, Barbara; Moretto, Paola; Parnigoni, Arianna; Caravà, Elena; Vitale, Daiana Luján; Alaniz, Laura Daniela; Viola, Manuela; Karousou, Evgenia; de Luca, Giancarlo; Hascall, Vincent C.; Passi, Alberto; Vigetti, Davide
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hyaluronan (HA) is one of the most prevalent glycosaminoglycans of the vascular extracellular matrix (ECM). Abnormal HA accumulation within blood vessel walls is associated with tissue inflammation and is prominent in most vascular pathological conditions such as atherosclerosis and restenosis. Hyaluronan synthase 2 (HAS2) is the main hyaluronan synthase enzyme involved in HA synthesis and uses cytosolic UDP-glucuronic acid and UDP-GlcNAc as substrates. The synthesis of UDP-glucuronic acid can alter the NAD+/NADH ratio via the enzyme UDP-glucose dehydrogenase, which oxidizes the alcohol group at C6 to the COO- group. Here, we show that HAS2 expression can be modulated by sirtuin 1 (SIRT1), the master metabolic sensor of the cell, belonging to the class of NAD+-dependent deacetylases. Our results revealed the following. 1) Treatments of human aortic smooth muscle cells (AoSMCs) with SIRT1 activators (SRT1720 and resveratrol) inhibit both HAS2 expression and accumulation of pericellular HA coats. 2) Tumor necrosis factor α (TNFα) induced HA-mediated monocyte adhesion and AoSMC migration, whereas SIRT1 activation prevented immune cell recruitment and cell motility by reducing the expression levels of the receptor for HA-mediated motility, RHAMM, and the HA-binding protein TNF-stimulated gene 6 protein (TSG6). 3) SIRT1 activation prevented nuclear translocation of NF-κB (p65), which, in turn, reduced the levels of HAS2–AS1, a long-noncoding RNA that epigenetically controls HAS2 mRNA expression. In conclusion, we demonstrate that both HAS2 expression and HA accumulation by AoSMCs are down-regulated by the metabolic sensor SIRT1.
Fil: Caon, Ilaria. Universitá Degli Studi Dell´insubria; Italia
Fil: Bartolini, Barbara. Universitá Degli Studi Dell´insubria; Italia
Fil: Moretto, Paola. Universitá Degli Studi Dell´insubria; Italia
Fil: Parnigoni, Arianna. Universitá Degli Studi Dell´insubria; Italia
Fil: Caravà, Elena. Universitá Degli Studi Dell´insubria; Italia
Fil: Vitale, Daiana Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina
Fil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina
Fil: Viola, Manuela. Universitá Degli Studi Dell´insubria; Italia
Fil: Karousou, Evgenia. Universitá Degli Studi Dell´insubria; Italia
Fil: de Luca, Giancarlo. Universitá Degli Studi Dell´insubria; Italia
Fil: Hascall, Vincent C.. Lerner Research Institute; Estados Unidos
Fil: Passi, Alberto. Universitá Degli Studi Dell´insubria; Italia
Fil: Vigetti, Davide. Universitá Degli Studi Dell´insubria; Italia
Materia
HAS2
HAS2-AS1
SMC
metabolic regulation
epigenetics
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/146353
Acceder
id CONICETDig_7e06037e92961383b75846e509c85475
oai_identifier_str oai:ri.conicet.gov.ar:11336/146353
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1Caon, IlariaBartolini, BarbaraMoretto, PaolaParnigoni, AriannaCaravà, ElenaVitale, Daiana LujánAlaniz, Laura DanielaViola, ManuelaKarousou, Evgeniade Luca, GiancarloHascall, Vincent C.Passi, AlbertoVigetti, DavideHAS2HAS2-AS1SMCmetabolic regulationepigeneticshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Hyaluronan (HA) is one of the most prevalent glycosaminoglycans of the vascular extracellular matrix (ECM). Abnormal HA accumulation within blood vessel walls is associated with tissue inflammation and is prominent in most vascular pathological conditions such as atherosclerosis and restenosis. Hyaluronan synthase 2 (HAS2) is the main hyaluronan synthase enzyme involved in HA synthesis and uses cytosolic UDP-glucuronic acid and UDP-GlcNAc as substrates. The synthesis of UDP-glucuronic acid can alter the NAD+/NADH ratio via the enzyme UDP-glucose dehydrogenase, which oxidizes the alcohol group at C6 to the COO- group. Here, we show that HAS2 expression can be modulated by sirtuin 1 (SIRT1), the master metabolic sensor of the cell, belonging to the class of NAD+-dependent deacetylases. Our results revealed the following. 1) Treatments of human aortic smooth muscle cells (AoSMCs) with SIRT1 activators (SRT1720 and resveratrol) inhibit both HAS2 expression and accumulation of pericellular HA coats. 2) Tumor necrosis factor α (TNFα) induced HA-mediated monocyte adhesion and AoSMC migration, whereas SIRT1 activation prevented immune cell recruitment and cell motility by reducing the expression levels of the receptor for HA-mediated motility, RHAMM, and the HA-binding protein TNF-stimulated gene 6 protein (TSG6). 3) SIRT1 activation prevented nuclear translocation of NF-κB (p65), which, in turn, reduced the levels of HAS2–AS1, a long-noncoding RNA that epigenetically controls HAS2 mRNA expression. In conclusion, we demonstrate that both HAS2 expression and HA accumulation by AoSMCs are down-regulated by the metabolic sensor SIRT1.Fil: Caon, Ilaria. Universitá Degli Studi Dell´insubria; ItaliaFil: Bartolini, Barbara. Universitá Degli Studi Dell´insubria; ItaliaFil: Moretto, Paola. Universitá Degli Studi Dell´insubria; ItaliaFil: Parnigoni, Arianna. Universitá Degli Studi Dell´insubria; ItaliaFil: Caravà, Elena. Universitá Degli Studi Dell´insubria; ItaliaFil: Vitale, Daiana Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Viola, Manuela. Universitá Degli Studi Dell´insubria; ItaliaFil: Karousou, Evgenia. Universitá Degli Studi Dell´insubria; ItaliaFil: de Luca, Giancarlo. Universitá Degli Studi Dell´insubria; ItaliaFil: Hascall, Vincent C.. Lerner Research Institute; Estados UnidosFil: Passi, Alberto. Universitá Degli Studi Dell´insubria; ItaliaFil: Vigetti, Davide. Universitá Degli Studi Dell´insubria; ItaliaAmerican Society for Biochemistry and Molecular Biology2020-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/146353Caon, Ilaria; Bartolini, Barbara; Moretto, Paola; Parnigoni, Arianna; Caravà, Elena; et al.; Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 295; 11; 3-2020; 3485-34960021-9258CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/lookup/doi/10.1074/jbc.RA119.011982info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.RA119.011982info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:08:26Zoai:ri.conicet.gov.ar:11336/146353instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:08:26.897CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1
title Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1
spellingShingle Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1
Caon, Ilaria
HAS2
HAS2-AS1
SMC
metabolic regulation
epigenetics
title_short Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1
title_full Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1
title_fullStr Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1
title_full_unstemmed Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1
title_sort Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1
dc.creator.none.fl_str_mv Caon, Ilaria
Bartolini, Barbara
Moretto, Paola
Parnigoni, Arianna
Caravà, Elena
Vitale, Daiana Luján
Alaniz, Laura Daniela
Viola, Manuela
Karousou, Evgenia
de Luca, Giancarlo
Hascall, Vincent C.
Passi, Alberto
Vigetti, Davide
author Caon, Ilaria
author_facet Caon, Ilaria
Bartolini, Barbara
Moretto, Paola
Parnigoni, Arianna
Caravà, Elena
Vitale, Daiana Luján
Alaniz, Laura Daniela
Viola, Manuela
Karousou, Evgenia
de Luca, Giancarlo
Hascall, Vincent C.
Passi, Alberto
Vigetti, Davide
author_role author
author2 Bartolini, Barbara
Moretto, Paola
Parnigoni, Arianna
Caravà, Elena
Vitale, Daiana Luján
Alaniz, Laura Daniela
Viola, Manuela
Karousou, Evgenia
de Luca, Giancarlo
Hascall, Vincent C.
Passi, Alberto
Vigetti, Davide
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HAS2
HAS2-AS1
SMC
metabolic regulation
epigenetics
topic HAS2
HAS2-AS1
SMC
metabolic regulation
epigenetics
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Hyaluronan (HA) is one of the most prevalent glycosaminoglycans of the vascular extracellular matrix (ECM). Abnormal HA accumulation within blood vessel walls is associated with tissue inflammation and is prominent in most vascular pathological conditions such as atherosclerosis and restenosis. Hyaluronan synthase 2 (HAS2) is the main hyaluronan synthase enzyme involved in HA synthesis and uses cytosolic UDP-glucuronic acid and UDP-GlcNAc as substrates. The synthesis of UDP-glucuronic acid can alter the NAD+/NADH ratio via the enzyme UDP-glucose dehydrogenase, which oxidizes the alcohol group at C6 to the COO- group. Here, we show that HAS2 expression can be modulated by sirtuin 1 (SIRT1), the master metabolic sensor of the cell, belonging to the class of NAD+-dependent deacetylases. Our results revealed the following. 1) Treatments of human aortic smooth muscle cells (AoSMCs) with SIRT1 activators (SRT1720 and resveratrol) inhibit both HAS2 expression and accumulation of pericellular HA coats. 2) Tumor necrosis factor α (TNFα) induced HA-mediated monocyte adhesion and AoSMC migration, whereas SIRT1 activation prevented immune cell recruitment and cell motility by reducing the expression levels of the receptor for HA-mediated motility, RHAMM, and the HA-binding protein TNF-stimulated gene 6 protein (TSG6). 3) SIRT1 activation prevented nuclear translocation of NF-κB (p65), which, in turn, reduced the levels of HAS2–AS1, a long-noncoding RNA that epigenetically controls HAS2 mRNA expression. In conclusion, we demonstrate that both HAS2 expression and HA accumulation by AoSMCs are down-regulated by the metabolic sensor SIRT1.
Fil: Caon, Ilaria. Universitá Degli Studi Dell´insubria; Italia
Fil: Bartolini, Barbara. Universitá Degli Studi Dell´insubria; Italia
Fil: Moretto, Paola. Universitá Degli Studi Dell´insubria; Italia
Fil: Parnigoni, Arianna. Universitá Degli Studi Dell´insubria; Italia
Fil: Caravà, Elena. Universitá Degli Studi Dell´insubria; Italia
Fil: Vitale, Daiana Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina
Fil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina
Fil: Viola, Manuela. Universitá Degli Studi Dell´insubria; Italia
Fil: Karousou, Evgenia. Universitá Degli Studi Dell´insubria; Italia
Fil: de Luca, Giancarlo. Universitá Degli Studi Dell´insubria; Italia
Fil: Hascall, Vincent C.. Lerner Research Institute; Estados Unidos
Fil: Passi, Alberto. Universitá Degli Studi Dell´insubria; Italia
Fil: Vigetti, Davide. Universitá Degli Studi Dell´insubria; Italia
description Hyaluronan (HA) is one of the most prevalent glycosaminoglycans of the vascular extracellular matrix (ECM). Abnormal HA accumulation within blood vessel walls is associated with tissue inflammation and is prominent in most vascular pathological conditions such as atherosclerosis and restenosis. Hyaluronan synthase 2 (HAS2) is the main hyaluronan synthase enzyme involved in HA synthesis and uses cytosolic UDP-glucuronic acid and UDP-GlcNAc as substrates. The synthesis of UDP-glucuronic acid can alter the NAD+/NADH ratio via the enzyme UDP-glucose dehydrogenase, which oxidizes the alcohol group at C6 to the COO- group. Here, we show that HAS2 expression can be modulated by sirtuin 1 (SIRT1), the master metabolic sensor of the cell, belonging to the class of NAD+-dependent deacetylases. Our results revealed the following. 1) Treatments of human aortic smooth muscle cells (AoSMCs) with SIRT1 activators (SRT1720 and resveratrol) inhibit both HAS2 expression and accumulation of pericellular HA coats. 2) Tumor necrosis factor α (TNFα) induced HA-mediated monocyte adhesion and AoSMC migration, whereas SIRT1 activation prevented immune cell recruitment and cell motility by reducing the expression levels of the receptor for HA-mediated motility, RHAMM, and the HA-binding protein TNF-stimulated gene 6 protein (TSG6). 3) SIRT1 activation prevented nuclear translocation of NF-κB (p65), which, in turn, reduced the levels of HAS2–AS1, a long-noncoding RNA that epigenetically controls HAS2 mRNA expression. In conclusion, we demonstrate that both HAS2 expression and HA accumulation by AoSMCs are down-regulated by the metabolic sensor SIRT1.
publishDate 2020
dc.date.none.fl_str_mv 2020-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/146353
Caon, Ilaria; Bartolini, Barbara; Moretto, Paola; Parnigoni, Arianna; Caravà, Elena; et al.; Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 295; 11; 3-2020; 3485-3496
0021-9258
CONICET Digital
CONICET
url http://hdl.handle.net/11336/146353
identifier_str_mv Caon, Ilaria; Bartolini, Barbara; Moretto, Paola; Parnigoni, Arianna; Caravà, Elena; et al.; Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 295; 11; 3-2020; 3485-3496
0021-9258
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/lookup/doi/10.1074/jbc.RA119.011982
info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.RA119.011982
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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