PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p

Autores
Brea, R.; Motiño, O.; Frances, Daniel Eleazar Antonio; García Monzón, C.; Vargas, J.; Fernández Velasco, M.; Boscá, L.; Casado, M.; Martin Sanz, Paloma; Agra, N.
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
MicroRNAs (miRNAs), small noncoding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key regulatory molecules in chronic liver diseases, whose end stage is hepatic fibrosis, a major global health burden. Pharmacological strategies for prevention or treatment of hepatic fibrosis are still limited, what makes it necessary to establish a better understanding of the molecular mechanisms underlying its pathogenesis. In this context, we have recently shown that cyclooxygenase-2 (COX-2) expression in hepatocytes restricts activation of hepatic stellate cells (HSCs), a pivotal event in the initiation and progression of hepatic fibrosis. Here, we evaluated the role of COX-2 in the regulation of a specific set of miRNAs on a mouse model of CCl4 and bile duct ligation (BDL)-induced liver fibrosis. Our results provide evidence that COX-2 represses miR-23a-5p and miR-28-5p expression in HSC. The decrease of miR-23a-5p and miR-28-5p expression promotes protection against fibrosis by decreasing the levels of pro-fibrogenic markers α-SMA and COL1A1 and increasing apoptosis of HSC. Moreover, we demonstrate that serum levels of miR-28-5p are decreased in patients with chronic liver disease. These results suggest a protective effect exerted by COX-2-derived prostanoids in the process of hepatofibrogenesis.
Fil: Brea, R.. Instituto de Investigaciones Biomédicas “Alberto Sols”; España
Fil: Motiño, O.. Instituto de Investigaciones Biomédicas “Alberto Sols”; España
Fil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: García Monzón, C.. Instituto de Investigación Sanitaria Princesa; España
Fil: Vargas, J.. Instituto de Investigación Sanitaria Princesa; España
Fil: Fernández Velasco, M.. Instituto de Investigación Hospital Universitario La Paz; España
Fil: Boscá, L.. Instituto de Investigaciones Biomédicas “Alberto Sols”; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares; España
Fil: Casado, M.. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares; España. Instituto de Biomedicina de Valencia; España
Fil: Martin Sanz, Paloma. Instituto de Investigaciones Biomédicas “Alberto Sols”; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares; España
Fil: Agra, N.. Instituto de Investigaciones Biomédicas “Alberto Sols”; España
Materia
COX-2
FIBROSIS
HSC
LIVER
MIRNAS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/87323
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/87323
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5pBrea, R.Motiño, O.Frances, Daniel Eleazar AntonioGarcía Monzón, C.Vargas, J.Fernández Velasco, M.Boscá, L.Casado, M.Martin Sanz, PalomaAgra, N.COX-2FIBROSISHSCLIVERMIRNAShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3MicroRNAs (miRNAs), small noncoding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key regulatory molecules in chronic liver diseases, whose end stage is hepatic fibrosis, a major global health burden. Pharmacological strategies for prevention or treatment of hepatic fibrosis are still limited, what makes it necessary to establish a better understanding of the molecular mechanisms underlying its pathogenesis. In this context, we have recently shown that cyclooxygenase-2 (COX-2) expression in hepatocytes restricts activation of hepatic stellate cells (HSCs), a pivotal event in the initiation and progression of hepatic fibrosis. Here, we evaluated the role of COX-2 in the regulation of a specific set of miRNAs on a mouse model of CCl4 and bile duct ligation (BDL)-induced liver fibrosis. Our results provide evidence that COX-2 represses miR-23a-5p and miR-28-5p expression in HSC. The decrease of miR-23a-5p and miR-28-5p expression promotes protection against fibrosis by decreasing the levels of pro-fibrogenic markers α-SMA and COL1A1 and increasing apoptosis of HSC. Moreover, we demonstrate that serum levels of miR-28-5p are decreased in patients with chronic liver disease. These results suggest a protective effect exerted by COX-2-derived prostanoids in the process of hepatofibrogenesis.Fil: Brea, R.. Instituto de Investigaciones Biomédicas “Alberto Sols”; EspañaFil: Motiño, O.. Instituto de Investigaciones Biomédicas “Alberto Sols”; EspañaFil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: García Monzón, C.. Instituto de Investigación Sanitaria Princesa; EspañaFil: Vargas, J.. Instituto de Investigación Sanitaria Princesa; EspañaFil: Fernández Velasco, M.. Instituto de Investigación Hospital Universitario La Paz; EspañaFil: Boscá, L.. Instituto de Investigaciones Biomédicas “Alberto Sols”; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares; EspañaFil: Casado, M.. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares; España. Instituto de Biomedicina de Valencia; EspañaFil: Martin Sanz, Paloma. Instituto de Investigaciones Biomédicas “Alberto Sols”; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares; EspañaFil: Agra, N.. Instituto de Investigaciones Biomédicas “Alberto Sols”; EspañaElsevier Science2018-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/87323Brea, R.; Motiño, O.; Frances, Daniel Eleazar Antonio; García Monzón, C.; Vargas, J.; et al.; PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p; Elsevier Science; Biochimica et Biophysica Acta - Molecular Basis of Disease; 1864; 2; 2-2018; 325-3370925-4439CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbadis.2017.11.001info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0925443917304155info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:06Zoai:ri.conicet.gov.ar:11336/87323instacron: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:34982025-09-03 09:49:06.849CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p
title PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p
spellingShingle PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p
Brea, R.
COX-2
FIBROSIS
HSC
LIVER
MIRNAS
title_short PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p
title_full PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p
title_fullStr PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p
title_full_unstemmed PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p
title_sort PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p
dc.creator.none.fl_str_mv Brea, R.
Motiño, O.
Frances, Daniel Eleazar Antonio
García Monzón, C.
Vargas, J.
Fernández Velasco, M.
Boscá, L.
Casado, M.
Martin Sanz, Paloma
Agra, N.
author Brea, R.
author_facet Brea, R.
Motiño, O.
Frances, Daniel Eleazar Antonio
García Monzón, C.
Vargas, J.
Fernández Velasco, M.
Boscá, L.
Casado, M.
Martin Sanz, Paloma
Agra, N.
author_role author
author2 Motiño, O.
Frances, Daniel Eleazar Antonio
García Monzón, C.
Vargas, J.
Fernández Velasco, M.
Boscá, L.
Casado, M.
Martin Sanz, Paloma
Agra, N.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv COX-2
FIBROSIS
HSC
LIVER
MIRNAS
topic COX-2
FIBROSIS
HSC
LIVER
MIRNAS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv MicroRNAs (miRNAs), small noncoding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key regulatory molecules in chronic liver diseases, whose end stage is hepatic fibrosis, a major global health burden. Pharmacological strategies for prevention or treatment of hepatic fibrosis are still limited, what makes it necessary to establish a better understanding of the molecular mechanisms underlying its pathogenesis. In this context, we have recently shown that cyclooxygenase-2 (COX-2) expression in hepatocytes restricts activation of hepatic stellate cells (HSCs), a pivotal event in the initiation and progression of hepatic fibrosis. Here, we evaluated the role of COX-2 in the regulation of a specific set of miRNAs on a mouse model of CCl4 and bile duct ligation (BDL)-induced liver fibrosis. Our results provide evidence that COX-2 represses miR-23a-5p and miR-28-5p expression in HSC. The decrease of miR-23a-5p and miR-28-5p expression promotes protection against fibrosis by decreasing the levels of pro-fibrogenic markers α-SMA and COL1A1 and increasing apoptosis of HSC. Moreover, we demonstrate that serum levels of miR-28-5p are decreased in patients with chronic liver disease. These results suggest a protective effect exerted by COX-2-derived prostanoids in the process of hepatofibrogenesis.
Fil: Brea, R.. Instituto de Investigaciones Biomédicas “Alberto Sols”; España
Fil: Motiño, O.. Instituto de Investigaciones Biomédicas “Alberto Sols”; España
Fil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: García Monzón, C.. Instituto de Investigación Sanitaria Princesa; España
Fil: Vargas, J.. Instituto de Investigación Sanitaria Princesa; España
Fil: Fernández Velasco, M.. Instituto de Investigación Hospital Universitario La Paz; España
Fil: Boscá, L.. Instituto de Investigaciones Biomédicas “Alberto Sols”; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares; España
Fil: Casado, M.. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares; España. Instituto de Biomedicina de Valencia; España
Fil: Martin Sanz, Paloma. Instituto de Investigaciones Biomédicas “Alberto Sols”; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares; España
Fil: Agra, N.. Instituto de Investigaciones Biomédicas “Alberto Sols”; España
description MicroRNAs (miRNAs), small noncoding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key regulatory molecules in chronic liver diseases, whose end stage is hepatic fibrosis, a major global health burden. Pharmacological strategies for prevention or treatment of hepatic fibrosis are still limited, what makes it necessary to establish a better understanding of the molecular mechanisms underlying its pathogenesis. In this context, we have recently shown that cyclooxygenase-2 (COX-2) expression in hepatocytes restricts activation of hepatic stellate cells (HSCs), a pivotal event in the initiation and progression of hepatic fibrosis. Here, we evaluated the role of COX-2 in the regulation of a specific set of miRNAs on a mouse model of CCl4 and bile duct ligation (BDL)-induced liver fibrosis. Our results provide evidence that COX-2 represses miR-23a-5p and miR-28-5p expression in HSC. The decrease of miR-23a-5p and miR-28-5p expression promotes protection against fibrosis by decreasing the levels of pro-fibrogenic markers α-SMA and COL1A1 and increasing apoptosis of HSC. Moreover, we demonstrate that serum levels of miR-28-5p are decreased in patients with chronic liver disease. These results suggest a protective effect exerted by COX-2-derived prostanoids in the process of hepatofibrogenesis.
publishDate 2018
dc.date.none.fl_str_mv 2018-02
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/11336/87323
Brea, R.; Motiño, O.; Frances, Daniel Eleazar Antonio; García Monzón, C.; Vargas, J.; et al.; PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p; Elsevier Science; Biochimica et Biophysica Acta - Molecular Basis of Disease; 1864; 2; 2-2018; 325-337
0925-4439
CONICET Digital
CONICET
url http://hdl.handle.net/11336/87323
identifier_str_mv Brea, R.; Motiño, O.; Frances, Daniel Eleazar Antonio; García Monzón, C.; Vargas, J.; et al.; PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p; Elsevier Science; Biochimica et Biophysica Acta - Molecular Basis of Disease; 1864; 2; 2-2018; 325-337
0925-4439
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbadis.2017.11.001
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0925443917304155
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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 13.13397

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