SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease

Autores
Mazzolini Rizzo, Guillermo Daniel; Atorrasagasti, María Catalina; Onorato, Agostina Mariana; Peixoto, Estanislao; Schlattjan, Martin; Sowa, Jan Peter; Sydor, Svenja; Gerken, Guido; Canbay, Ali
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mechanisms that control progression from simple steatosis to steato-hepatitis and fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are unknown. SPARC, a secreted matricellular protein, is over-expressed in the liver under chronic injury. Contribution of SPARC accumulation to disease severity is largely unknown in NAFLD. We assessed the hypothesis that SPARC is increased in livers with more necrosis and inflammation and could be associated with more fibrosis. qrt-PCR, immunohistochemistry, and ELISA were employed to localize and quantify changes in SPARC in 62 morbidly obese patients with NAFLD/NASH and in a mouse model of diet-induced-NASH. Results were correlated with the severity of NAFLD/NASH. In obese patients 2 subgroups were identified with either high SPARC expression (n = 16) or low SPARC expression (n = 46) in the liver, with a cutoff of 1.2 fold expression. High expression of SPARC paralleled hepatocellular damage and increased mRNA expression of pro-fibrogenic factors in the liver. In line with these findings, in the NASH animal model SPARC knockout mice were protected from inflammatory injury, and showed less inflammation and fibrosis. Hepatic SPARC expression is associated with liver injury and fibrogenic processes in NAFLD. SPARC has potential as preventive or therapeutic target in NAFLD patients.
Fil: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Atorrasagasti, María Catalina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Onorato, Agostina Mariana. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Peixoto, Estanislao. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Schlattjan, Martin. Universitat Essen; Alemania
Fil: Sowa, Jan Peter. Universitat Essen; Alemania
Fil: Sydor, Svenja. Universitat Essen; Alemania
Fil: Gerken, Guido. Universitat Essen; Alemania
Fil: Canbay, Ali. Universitat Essen; Alemania
Materia
SPARC
NAFLD
NASH
OBESITY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/92223
Acceder
id CONICETDig_0f39cbf981b09305fcbc10ea229e55a7
oai_identifier_str oai:ri.conicet.gov.ar:11336/92223
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver diseaseMazzolini Rizzo, Guillermo DanielAtorrasagasti, María CatalinaOnorato, Agostina MarianaPeixoto, EstanislaoSchlattjan, MartinSowa, Jan PeterSydor, SvenjaGerken, GuidoCanbay, AliSPARCNAFLDNASHOBESITYhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Mechanisms that control progression from simple steatosis to steato-hepatitis and fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are unknown. SPARC, a secreted matricellular protein, is over-expressed in the liver under chronic injury. Contribution of SPARC accumulation to disease severity is largely unknown in NAFLD. We assessed the hypothesis that SPARC is increased in livers with more necrosis and inflammation and could be associated with more fibrosis. qrt-PCR, immunohistochemistry, and ELISA were employed to localize and quantify changes in SPARC in 62 morbidly obese patients with NAFLD/NASH and in a mouse model of diet-induced-NASH. Results were correlated with the severity of NAFLD/NASH. In obese patients 2 subgroups were identified with either high SPARC expression (n = 16) or low SPARC expression (n = 46) in the liver, with a cutoff of 1.2 fold expression. High expression of SPARC paralleled hepatocellular damage and increased mRNA expression of pro-fibrogenic factors in the liver. In line with these findings, in the NASH animal model SPARC knockout mice were protected from inflammatory injury, and showed less inflammation and fibrosis. Hepatic SPARC expression is associated with liver injury and fibrogenic processes in NAFLD. SPARC has potential as preventive or therapeutic target in NAFLD patients.Fil: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Atorrasagasti, María Catalina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Onorato, Agostina Mariana. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Peixoto, Estanislao. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Schlattjan, Martin. Universitat Essen; AlemaniaFil: Sowa, Jan Peter. Universitat Essen; AlemaniaFil: Sydor, Svenja. Universitat Essen; AlemaniaFil: Gerken, Guido. Universitat Essen; AlemaniaFil: Canbay, Ali. Universitat Essen; AlemaniaNature Publishing Group2018-12info: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/11336/92223Mazzolini Rizzo, Guillermo Daniel; Atorrasagasti, María Catalina; Onorato, Agostina Mariana; Peixoto, Estanislao; Schlattjan, Martin; et al.; SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease; Nature Publishing Group; Scientific Reports; 8; 1; 12-2018; 1-112045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41598-017-18981-9info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-017-18981-9info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:09:21Zoai:ri.conicet.gov.ar:11336/92223instacron: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 10:09:21.345CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
title SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
spellingShingle SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
Mazzolini Rizzo, Guillermo Daniel
SPARC
NAFLD
NASH
OBESITY
title_short SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
title_full SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
title_fullStr SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
title_full_unstemmed SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
title_sort SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
dc.creator.none.fl_str_mv Mazzolini Rizzo, Guillermo Daniel
Atorrasagasti, María Catalina
Onorato, Agostina Mariana
Peixoto, Estanislao
Schlattjan, Martin
Sowa, Jan Peter
Sydor, Svenja
Gerken, Guido
Canbay, Ali
author Mazzolini Rizzo, Guillermo Daniel
author_facet Mazzolini Rizzo, Guillermo Daniel
Atorrasagasti, María Catalina
Onorato, Agostina Mariana
Peixoto, Estanislao
Schlattjan, Martin
Sowa, Jan Peter
Sydor, Svenja
Gerken, Guido
Canbay, Ali
author_role author
author2 Atorrasagasti, María Catalina
Onorato, Agostina Mariana
Peixoto, Estanislao
Schlattjan, Martin
Sowa, Jan Peter
Sydor, Svenja
Gerken, Guido
Canbay, Ali
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv SPARC
NAFLD
NASH
OBESITY
topic SPARC
NAFLD
NASH
OBESITY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Mechanisms that control progression from simple steatosis to steato-hepatitis and fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are unknown. SPARC, a secreted matricellular protein, is over-expressed in the liver under chronic injury. Contribution of SPARC accumulation to disease severity is largely unknown in NAFLD. We assessed the hypothesis that SPARC is increased in livers with more necrosis and inflammation and could be associated with more fibrosis. qrt-PCR, immunohistochemistry, and ELISA were employed to localize and quantify changes in SPARC in 62 morbidly obese patients with NAFLD/NASH and in a mouse model of diet-induced-NASH. Results were correlated with the severity of NAFLD/NASH. In obese patients 2 subgroups were identified with either high SPARC expression (n = 16) or low SPARC expression (n = 46) in the liver, with a cutoff of 1.2 fold expression. High expression of SPARC paralleled hepatocellular damage and increased mRNA expression of pro-fibrogenic factors in the liver. In line with these findings, in the NASH animal model SPARC knockout mice were protected from inflammatory injury, and showed less inflammation and fibrosis. Hepatic SPARC expression is associated with liver injury and fibrogenic processes in NAFLD. SPARC has potential as preventive or therapeutic target in NAFLD patients.
Fil: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Atorrasagasti, María Catalina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Onorato, Agostina Mariana. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Peixoto, Estanislao. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Schlattjan, Martin. Universitat Essen; Alemania
Fil: Sowa, Jan Peter. Universitat Essen; Alemania
Fil: Sydor, Svenja. Universitat Essen; Alemania
Fil: Gerken, Guido. Universitat Essen; Alemania
Fil: Canbay, Ali. Universitat Essen; Alemania
description Mechanisms that control progression from simple steatosis to steato-hepatitis and fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are unknown. SPARC, a secreted matricellular protein, is over-expressed in the liver under chronic injury. Contribution of SPARC accumulation to disease severity is largely unknown in NAFLD. We assessed the hypothesis that SPARC is increased in livers with more necrosis and inflammation and could be associated with more fibrosis. qrt-PCR, immunohistochemistry, and ELISA were employed to localize and quantify changes in SPARC in 62 morbidly obese patients with NAFLD/NASH and in a mouse model of diet-induced-NASH. Results were correlated with the severity of NAFLD/NASH. In obese patients 2 subgroups were identified with either high SPARC expression (n = 16) or low SPARC expression (n = 46) in the liver, with a cutoff of 1.2 fold expression. High expression of SPARC paralleled hepatocellular damage and increased mRNA expression of pro-fibrogenic factors in the liver. In line with these findings, in the NASH animal model SPARC knockout mice were protected from inflammatory injury, and showed less inflammation and fibrosis. Hepatic SPARC expression is associated with liver injury and fibrogenic processes in NAFLD. SPARC has potential as preventive or therapeutic target in NAFLD patients.
publishDate 2018
dc.date.none.fl_str_mv 2018-12
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/11336/92223
Mazzolini Rizzo, Guillermo Daniel; Atorrasagasti, María Catalina; Onorato, Agostina Mariana; Peixoto, Estanislao; Schlattjan, Martin; et al.; SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease; Nature Publishing Group; Scientific Reports; 8; 1; 12-2018; 1-11
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/92223
identifier_str_mv Mazzolini Rizzo, Guillermo Daniel; Atorrasagasti, María Catalina; Onorato, Agostina Mariana; Peixoto, Estanislao; Schlattjan, Martin; et al.; SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease; Nature Publishing Group; Scientific Reports; 8; 1; 12-2018; 1-11
2045-2322
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.nature.com/articles/s41598-017-18981-9
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-017-18981-9
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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
_version_ 1842270077104160768
score 13.13397

Publicaciones similares