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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/146353
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oai:ri.conicet.gov.ar:11336/146353 |
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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 Técnicas2025-09-29T09:40:01Zoai: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:34982025-09-29 09:40:01.922CONICET 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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1844613266137939968 |
score |
13.070432 |